The Megyn Kelly Show - A Deep Dive Into Alzheimer's and Disturbing New Scientific Findings, with Dr. Dale Bredesen, Dr. Matthew Schrag, and Charles Piller ｜ Ep. 373

00:00:00.540 Welcome to The Megyn Kelly Show, your home for open, honest, and provocative conversations.

00:00:11.660 Hey everyone, I'm Megyn Kelly. Welcome to The Megyn Kelly Show.

00:00:15.500 Tomorrow, we're going to tackle the latest developments on this FBI search of former

00:00:20.020 President Donald Trump's Mar-a-Lago home, and there is a lot to go over.

00:00:25.340 A lot's happened since I was last on the air on Thursday, and I've got a lot to say about it.

00:00:29.080 But today, we've got an amazing show for you on a different subject, and I'm really

00:00:33.540 excited about this program.

00:00:35.180 We've got the first in-depth broadcast interview with a whistleblower who discovered that one

00:00:40.060 of the most influential studies in Alzheimer's research may have been a fraud.

00:00:46.280 It is not an understatement to say that Dr. Matthew Schrag's discovery has caused headlines

00:00:51.000 around the world.

00:00:53.160 Every major media outlet has covered this.

00:00:55.800 And if that turns out to be true, it means about a billion dollars in U.S. taxpayer money

00:01:01.780 used for Alzheimer's research over the past 16 years may have been for nothing.

00:01:06.460 Not to mention, if you know a loved one dealing with Alzheimer's, you know that it's a nightmare

00:01:11.760 disease and we have no time to waste.

00:01:14.640 So for 16 plus years, we may have been focusing our energy in the wrong direction if this seminal

00:01:21.300 article and study was fraudulent.

00:01:25.120 This disease affects roughly 6 million Americans, a number that's expected to double in the next

00:01:31.900 25 years.

00:01:33.020 Double.

00:01:33.920 And there is no treatment that cures it.

00:01:36.440 So what Dr. Schrag discovered about this seminal study is a very, very big deal.

00:01:43.420 He will walk us through what he discovered, what it means for Alzheimer's research, the

00:01:47.800 pushback he's received, and whether he now fears for his career.

00:01:53.340 Then we will be joined by an investigative journalist for Science Magazine who took a close look at the

00:01:58.880 doctors who authored this controversial study, the funding they received, and what happened

00:02:04.880 after Dr. Schrag, the whistleblower, notified the National Institute of Health of his troubling

00:02:11.560 discovery.

00:02:13.540 And then we will welcome back renowned brain health expert, Dr. Dale Bredesen.

00:02:18.420 He has thoughts on all of this, what it means about medicine, and also specific steps that you can

00:02:24.920 take today if you would like to help boost brain memory.

00:02:28.940 All hope is not lost if you become a sufferer of dementia.

00:02:33.860 There are certainly forms of Alzheimer's that there's very little you can do about, but there

00:02:38.020 are forms of dementia that you can help stave off and improve if you happen to become subject to

00:02:45.840 them.

00:02:46.540 But we begin today with Dr. Matthew Schrag.

00:02:49.720 He's a neuroscientist at Vanderbilt University, and it's our pleasure to welcome him here.

00:02:54.920 to the program.

00:02:59.780 Welcome, Dr. Schrag.

00:03:00.800 Great to have you.

00:03:02.420 Hi, Megan.

00:03:03.220 Thanks for the invitation.

00:03:04.460 I'm looking forward to our conversation.

00:03:07.100 Me too.

00:03:07.680 And may I just say, I admire your courage and your willingness to just say what's real based on your

00:03:14.320 own independent scientific findings as opposed to what you know is going to go over well and what

00:03:19.820 people want to hear.

00:03:21.600 Yeah, I appreciate that.

00:03:23.200 You know, I'm a physician and I see patients suffering with this disease day in and day

00:03:27.520 out.

00:03:28.260 And there really is no judgment call here.

00:03:30.580 You have to you have to speak the truth.

00:03:32.460 So you are a very accomplished man in terms of your own medical history and your resume,

00:03:39.840 neurology residency and fellowship at Yale, vascular neurology fellowship at Vanderbilt,

00:03:45.200 board certified vascular neurologist, assistant professor of neurology at Vanderbilt University

00:03:49.340 Medical Center.

00:03:50.040 And your research focuses on how cerebral amyloid angiopathy contributes to cognitive impairment

00:03:57.000 in Alzheimer's disease.

00:03:57.960 You're an expert in Alzheimer's.

00:03:59.260 What causes it?

00:04:00.080 What's likely to cause it?

00:04:01.040 And so on.

00:04:02.060 So you're there at at Vanderbilt doing your thing in medicine, teaching, researching.

00:04:08.740 And this all got started because, as I understand it, you got a call to take a look at it at

00:04:17.440 an Alzheimer's drug.

00:04:19.420 And they said, could you take a look at this and see whether this is actually likely to

00:04:24.640 help people?

00:04:25.080 Because it's been approved by the FDA and a bunch of scientists were like, we don't we're

00:04:30.900 not sure we don't we're not sure we like this drug.

00:04:32.880 We're not sure this should have been approved.

00:04:34.440 What do you think?

00:04:35.040 So far, do I have my facts right?

00:04:37.940 Well, I, along with quite a lot of other scientists, expressed some concerns about

00:04:43.580 Aducanumab over a year ago now.

00:04:47.380 And I think that as a community of scientists, we're very committed to making sure that drugs

00:04:53.440 that we offer to our patients deliver on the promise, especially if they're dangerous

00:04:59.000 and especially if they're expensive.

00:05:00.440 Um, so that was my, um, first exposure to national media was simply speaking out along

00:05:07.120 with quite a lot of other scientists about concerns about, uh, Biogen's Aducanumab.

00:05:12.420 And that led to-

00:05:13.640 Okay, and that's also known as Aduhelm?

00:05:15.300 Correct.

00:05:15.840 The trade name is Aduhelm.

00:05:17.740 Okay.

00:05:18.360 All right.

00:05:18.540 So let me just, we're going to go through it in baby steps so people can follow.

00:05:21.320 And, and fear not audience, because I have done the deep dive as a lay person so that

00:05:26.240 we can, I can walk us through this in a way I think everybody's going to get it.

00:05:29.040 Okay.

00:05:29.460 So, um, there was a July, 2021 New York Times article on Aduhelm, this drug, it was approved

00:05:35.520 by the FDA and this thing attacks amyloids.

00:05:39.060 And there was a, there's just briefly explain what's an amyloid.

00:05:43.020 So 115 years ago when Dr. Alzheimer's defined what Alzheimer's disease is, he saw two things

00:05:50.200 happening in the brain.

00:05:51.320 One is the accumulation of huge numbers of what he called plaques in which we now know

00:05:56.440 is formed of this, a little tiny peptide called beta amyloid, which is sticky and has formed

00:06:02.320 giant clumps, uh, in the brain.

00:06:05.120 And the second thing he discovered were tangles, uh, within the neurons that caused them to not

00:06:10.700 be able to fire properly anymore.

00:06:12.820 Uh, and so amyloid, the plaques have been proposed to be the problem that starts off this

00:06:19.580 disease, um, and the drug tried to remove those plaques.

00:06:24.400 So just stop you there.

00:06:25.600 So what they found in the brain was amyloids or plaques and tangles.

00:06:30.400 And we knew that they were associated with Alzheimer's disease, that they were characteristic

00:06:35.080 of Alzheimer's, but we did not know that whether they were a cause.

00:06:39.220 That's, that's the next step to the plaques that we find in the brains of deceased Alzheimer's

00:06:45.040 patients actually cause Alzheimer's.

00:06:47.900 And that's a much bigger leap.

00:06:49.180 And even right at this moment, we don't know the answer, but that's where our story's going.

00:06:54.380 That's right.

00:06:54.860 So in the early nineties, um, during the genetic revolution, when we started understanding the

00:07:00.220 genetics of some rare forms of Alzheimer's disease, this became a leading theory that the

00:07:05.100 plaques themselves were the driver, the thing that starts, uh, the process of neurodegeneration

00:07:10.820 and Alzheimer's disease.

00:07:13.020 Okay.

00:07:13.640 So this drug Adjahelm, um, which was by Biogen, the drug maker was supposed to address these

00:07:22.000 plaques.

00:07:22.900 And yet a bunch of doctors, including yourself, were very critical of this saying the proof

00:07:27.740 is not there that it does that.

00:07:29.300 And the proof is not there that the, the costs are outweighed by the benefits.

00:07:35.320 Now, as I understand it from the New York times article, the FDA approved this drug despite

00:07:39.520 a council of senior agency officials resoundingly agreeing two months earlier at the FDA, there

00:07:45.500 was not enough evidence that this drug worked and they wanted another clinical trial.

00:07:49.320 They said otherwise people could be harmed.

00:07:51.020 But then on June 7th of 21, FDA greenlit the drug anyway, scathing rebuke from Alzheimer's

00:07:57.780 disease experts like you calls for an investigation into how that thing got approved.

00:08:02.340 It costs $56,000 a year, this drug.

00:08:05.880 And the FDA just defended itself saying we didn't lower our standards.

00:08:09.660 Uh, look that we subjected it to what's called accelerated approval where serious disease

00:08:14.140 is faced with very few treatment options.

00:08:17.440 It's basically like, you know, the long shot, the Hail Mary and the drug flopped.

00:08:22.540 Okay.

00:08:23.100 So you were one of the scientists pulled in on there and you again spoke honestly and said,

00:08:27.400 serious questions, serious questions.

00:08:30.420 And then a different group of scientists, I think, or maybe it's the same, came back

00:08:34.580 to you about a different drug made by cassava sciences.

00:08:38.820 Is that how you pronounce it?

00:08:39.760 Correct.

00:08:40.620 Cassava sciences.

00:08:41.660 This one was called semifilum?

00:08:45.780 Semifilum.

00:08:46.400 Yeah.

00:08:47.340 Semifilum.

00:08:47.960 Okay.

00:08:48.960 Now this one, once again, these scientists are concerned.

00:08:52.840 And they look, it's got similar problems in that the early results seemed a little suspect.

00:08:58.720 The FDA approved it to go forward to be tested in human beings.

00:09:01.920 And these scientists were concerned that people were going to be harmed.

00:09:04.960 This drug company was worth nearly 5 billion bucks last summer.

00:09:08.360 So they were doing pretty darn well.

00:09:09.980 And they wanted someone like you to take a hard look at that drug and see if, in fact,

00:09:16.020 it should be used to treat Alzheimer's.

00:09:18.900 So that's where our story really starts to begin.

00:09:23.120 So tell us what happened of note while you were taking a look at that drug.

00:09:26.740 So this is outside of my work with Vanderbilt University.

00:09:31.300 I was contracted by an attorney representing a number of scientists who had concerns that

00:09:37.600 the data that was used to justify moving this drug into clinical trials had a pattern

00:09:45.260 of artifacts in it that was concerning.

00:09:48.060 And then one raised concerns that perhaps there was some manipulation of the data or research

00:09:54.580 misconduct.

00:09:55.160 And I was asked to come in and independently look at their concerns and to look at the

00:10:00.520 papers more broadly and give another independent voice regarding what the basic science data

00:10:08.260 looked like.

00:10:09.300 And what we found was a pervasive pattern of these red flags.

00:10:13.860 There's some limitations about what you can say just from published information.

00:10:18.820 And so it's very hard to conclusively state that there's a fraud or that there's misconduct

00:10:24.220 there, but certainly there is a pervasive pattern of things you wouldn't expect in the data.

00:10:30.480 And I think journalists and photographers look at a lot of the visual images the same way we do.

00:10:37.020 The data that this company was producing ends with a photograph of an experiment.

00:10:41.520 And the photographs just didn't look natural.

00:10:45.200 And that was the starting point for us to say perhaps this needed a closer look and that some

00:10:49.880 regulatory bodies should make a priority to review this, especially with patients being exposed to the drug.

00:10:57.100 So how does a doctor named Sylvain Lesney appear in your world in this time?

00:11:05.920 Well, it's almost happenstance.

00:11:08.180 At the time, I was looking at ways of doing a forensic analysis on these images.

00:11:16.680 And I encountered his paper partly because it was a prominent paper, but some people who do research

00:11:27.160 integrity work had flagged a couple of his other lower profile papers.

00:11:32.000 And, you know, it just caught my eye that the images in his paper look similar to the ones I had been

00:11:37.320 investigating and just, like I said previously, didn't look natural.

00:11:40.780 They sort of had the kinds of things that, you know, look like Photoshop type changes in them.

00:11:47.140 And that prompted me to take a closer look, especially because as I reviewed his body of work,

00:11:52.440 a number of his works were enormously influential.

00:11:57.040 So his name, again, Sylvain, I don't know how you pronounce it, to be honest, Lesney, L-E-S-N-E,

00:12:03.040 French guy, neuroscientist, associate professor at the University of Minnesota.

00:12:07.100 And he had sort of the mentorship of a very important doctor named Dr. Karen Ash,

00:12:15.640 who's also a neuroscientist and professor at the University of Minnesota.

00:12:20.000 She's a full professor.

00:12:21.600 So this guy, Dr. Lesney, the French guy, but he's here in America,

00:12:25.980 you start to see some of the images that he's been using in papers that he's been putting out

00:12:31.880 over the past couple of decades.

00:12:33.240 And they look, as my 11-year-old daughter would say, sus.

00:12:38.140 They look sussy baka, as she might explain. 1.00

00:12:42.280 And you start to dig a little deeper.

00:12:45.820 And this guy, along with his mentor, Dr. Karen Ash at the University of Minnesota,

00:12:49.880 are the authors of the seminal study from 2006 on Alzheimer's and what causes it.

00:12:58.380 And in particular, you know, we'll get it to exactly what their theory was.

00:13:01.700 But basically, that paper that they wrote in 2006 has been like the genesis of studies

00:13:09.280 on what causes Alzheimer's and how we should treat Alzheimer's ever since.

00:13:13.820 And they've gotten billions of dollars in funding to pursue this line of research and so on.

00:13:18.900 And what you basically said was, this 2006 study they did together has got equally problematic images

00:13:27.560 to the ones I found Dr. Lesney using in virtually every study he's been attached to ever since.

00:13:35.800 Yeah, that's right.

00:13:36.960 The 2006 was an interesting moment for the amyloid hypothesis because it was one of the times 1.00

00:13:45.320 when it was coming under the hardest scrutiny because the first clinical trials had started to fail.

00:13:51.600 And so the hypothesis was starting to be reformulated to focus on something called an oligomer.

00:13:58.140 Instead of saying that the whole clump of sticky beta amyloid protein was the problem,

00:14:03.200 they assumed that before you had a giant clump, you must have had a very small clump

00:14:07.600 that grouped together to form these plaques.

00:14:10.220 And these very small clumps we call oligomers have become the focus of a lot of Alzheimer's research

00:14:15.860 because they think this is what's actually conferring the toxicity that's damaging the neurons.

00:14:21.320 And this study was very influential at advancing that hypothesis.

00:14:27.660 Okay, so what they did together at the University of Minnesota back then, 2006,

00:14:32.500 as I understand it, is she, Dr. Karen Ashe, who again was, and I assume right now remains well-respected,

00:14:41.320 had these mice that she developed.

00:14:45.440 And they basically took these mice and they took something out of, they were like purified mice,

00:14:52.300 and they took something out of these mice and injected it into rats.

00:14:55.500 And those rats who had been perfectly able to find the treat in the maze by going through door two

00:15:01.860 suddenly could no longer remember how to find door two and get the treat.

00:15:06.600 Like they'd been fine on Monday, then she injected this stuff in them,

00:15:09.820 and then on Tuesday, they couldn't find the treat.

00:15:13.240 Is that pedestrian explanation about right?

00:15:15.740 No, that's perfectly okay.

00:15:17.160 They isolated these oligomers, in this case a very specific one, 1.00

00:15:21.120 which was a clump of 12 strands of this little tiny beta amyloid protein that they thought was the silver bullet.

00:15:29.240 And they found that when they put it into mice or to rats, rather,

00:15:32.080 that they could no longer remember as well as they had before.

00:15:36.080 And so they were like, this is the aha moment that proves,

00:15:39.260 to go back to our original, the opening of our discussion, the plaques cause Alzheimer's.

00:15:44.560 It certainly was an important part of showing that the oligomers contributed to the toxicity.

00:15:51.580 And importantly, which had never been shown, at least robustly before,

00:15:55.680 they showed that the plaque caused memory problems.

00:15:59.120 In the past, it had always been a problem with the amyloid hypothesis,

00:16:02.060 is that the plaques don't correlate very strongly with memory.

00:16:05.380 By the time patients have memory problems, they have a massive amount of plaques in their brain.

00:16:09.520 And that was a real problem for the hypothesis that this paper started to unravel.

00:16:15.280 Because all along, Alzheimer's researchers, if you zoom out to the 30,000 foot level,

00:16:20.760 have been debating, well, you know, do the plaques cause memory problems?

00:16:25.280 What actually causes Alzheimer's?

00:16:26.740 Is it the plaques? Is it something else?

00:16:28.500 There are other theories out there besides the plaques being sort of at the center.

00:16:34.300 And, you know, Dr. Ash and Dr. Lesney were in the plaques do cause it and do cause memory problems lane.

00:16:41.500 But there have been other scientists in these other lanes saying,

00:16:43.800 you're wrong, we can't replicate your results,

00:16:47.500 and we would like more funding in our lanes for research on these other potential causes.

00:16:53.520 Yeah, it had been a huge problem trying to get funding to alternate theories.

00:17:00.240 The amyloid hypothesis, particularly in the mid-2000s, was so dominant and continued to be dominant

00:17:05.460 that a lot of very respected researchers outside of that mainstream thought process

00:17:13.620 complained that they had difficulty getting their ideas adequately funded to test them.

00:17:18.440 So their 2006 paper saying these oligomers, you know, the small sort of, I don't know how to phrase it,

00:17:27.680 but that the oligomers are in the lane of the plaques cause Alzheimer's.

00:17:33.000 And we're advancing that theory with this study.

00:17:35.600 That's essentially what they said they proved.

00:17:38.000 That's right.

00:17:39.060 And there were obviously quite a number of other scientists that were also in that lane.

00:17:43.100 And so the entire hypothesis certainly doesn't hinge on this one paper,

00:17:46.780 but it was a hugely influential paper and a core piece of the foundation

00:17:50.580 of this oligomer hypothesis going forward.

00:17:53.420 And it created a lot of momentum for the hypothesis.

00:17:55.700 And created, as I understand it, the NIH funding for that type of research was,

00:18:01.780 according to our research, zero.

00:18:04.020 And then now it's up to $287 million a year, a year.

00:18:09.780 So it was important.

00:18:11.880 It definitely had a role in increasing funding on, you know, pursuing this line.

00:18:16.340 Again, Dr. Karen Ash, very well respected.

00:18:18.900 Less need less known.

00:18:20.640 So you figure out, oh my God, I mean, you must have, just as a personal matter,

00:18:24.180 you must have had sort of an holy cow moment when you realized this study

00:18:29.660 had what you believe to be falsified images in it.

00:18:34.340 Yeah, I think, you know, we tend to respect our colleagues implicitly in this business.

00:18:41.400 And I think that scientists on a whole pride ourselves on being very trustworthy.

00:18:47.260 So it's sort of hard to believe at first blush.

00:18:50.080 And I think, you know, I went back to it over and over again.

00:18:54.180 Trying to understand how this might have happened.

00:18:57.400 And, you know, I think got to the point where the concerns were strong enough

00:19:01.660 that something had to be said about it.

00:19:04.260 You know, one, and I understand because I've looked at the images now

00:19:07.840 and there's all sorts of questions about these pictures and what they show

00:19:11.260 and have they been manipulated.

00:19:12.480 And it seems to be kind of generally accepted right now

00:19:15.680 that they were manipulated by this guy, Lesney.

00:19:18.160 But one of my questions was, you know, just because let's assume that the photographs

00:19:22.440 submitted were doctored.

00:19:25.960 How does that undermine the study?

00:19:28.380 Like she still got rats who couldn't find the treats.

00:19:31.420 So like that wouldn't be in the picture.

00:19:34.600 Right.

00:19:35.160 Well, so there's only certain components of a study that you can subject to forensic analysis.

00:19:41.360 Right.

00:19:41.940 So it's very hard to look at charts that show the response time

00:19:46.380 and the behaviors of mice and rats and conduct a forensic analysis on that

00:19:52.080 without a team who has access to the original data.

00:19:54.880 But photographs in this case are the original data.

00:19:58.460 They're a sampling of the original data.

00:20:00.180 It's not all of it.

00:20:01.000 And one has to worry that if the components that we're being shown have problems in them,

00:20:10.860 it's possible that it's the tip of the iceberg and that other elements of the study

00:20:14.880 that can't be as easily analyzed also have problems.

00:20:18.700 And that's why it's so important for regulatory bodies to take these red flags seriously when

00:20:22.960 we see them, because there may be other issues that are harder to see in the studies as well.

00:20:28.100 What I understand that you use something called the Western blot,

00:20:33.080 widely used lab imaging technique, and it helps one see protein bands.

00:20:39.180 Now, when you were looking at them, I saw some of them and you could see some had just been

00:20:43.980 they look like obvious copies from a different study.

00:20:47.940 Is that what you believe this guy Lesney did?

00:20:50.100 He just kind of said, here's one that shows what we're looking for, you know,

00:20:54.000 and what is like what are these blobs that we're seeing on the screen showing us?

00:20:58.100 So this is one of the ways that we study proteins.

00:21:03.160 We separate them out in a gelatin so that the larger ones separate from the smaller ones.

00:21:09.340 And how big that black blot is in each one of those little marks,

00:21:14.100 we can measure how black that is.

00:21:15.920 And that tells us how much is in the sample.

00:21:18.860 And it helps us to understand if the amount of the protein is changing

00:21:22.580 with the disease state.

00:21:25.020 It helps us understand how big the protein is.

00:21:27.280 So when it's clumping together, we can measure the size of the protein using this technique.

00:21:32.000 So it's a very excellent technique for understanding the behavior of a protein within,

00:21:38.140 within, in this case, the brain.

00:21:39.900 But the end result is a photograph.

00:21:43.920 And just like, you know, you can Photoshop a photograph and make it look different than

00:21:50.300 the original one was, the same thing can happen with the end result of this Western blot,

00:21:55.700 which is just a photograph.

00:21:56.760 And in the old days, we used film.

00:21:57.940 And now, of course, we use digital images and process them with Photoshop.

00:22:02.760 Is it a photograph of the protein found in the rats brains after they were injected by

00:22:08.940 Dr. Ash?

00:22:10.320 So in this case, they're showing you the purification steps.

00:22:14.620 They're verifying the purification of the protein that they're injecting into the mice

00:22:18.940 or to the rats, rather.

00:22:20.560 So this comes from her mouse model, most of these images.

00:22:23.900 And she's showing you, the two of them are showing you the range of proteins that are being

00:22:30.340 identified, different forms of beta amyloid that are being identified within this mouse's

00:22:35.040 brain.

00:22:35.980 And then they, I put it through a series of isolation steps to purify out the one that

00:22:40.500 they're looking for.

00:22:42.280 So if the protein that's purified is not what they say it is, then it's very hard to interpret

00:22:47.480 the rat's behavior.

00:22:50.820 Is there any way she had no idea?

00:22:53.440 I mean, I, I don't understand because he's gotten all the flack, this guy, Lesney, and she's

00:22:58.380 still sort of sitting there at the university of Minnesota.

00:23:00.660 And apparently he's gone underground.

00:23:01.800 He hasn't spoken to anybody.

00:23:02.920 She's given four different statements that get, that are getting increasingly defensive,

00:23:06.300 but is there any way she would not have known?

00:23:10.140 I don't know.

00:23:11.280 You know, I don't know her personally, but I've known her work for a very long time and

00:23:16.160 she's a highly respected scientist.

00:23:17.960 And I'll tell you that I did analyze a number of her studies that did not involve Dr.

00:23:24.880 Lesney.

00:23:25.840 And I did not find the same pervasive pattern of, of changes there.

00:23:30.200 They seem to segregate with the studies that she coauthored with Dr.

00:23:34.600 Lesney.

00:23:35.960 That the degree to which she was aware of this or should have been aware of this, I simply

00:23:40.200 don't know.

00:23:42.200 The, she originally told NBC news, her wish is that the study be retracted in its entirety.

00:23:48.420 She said, quote, having worked for decades to understand the cause of Alzheimer's disease

00:23:52.460 so that better treatments can be found for patients.

00:23:55.100 It is devastating to discover that a coworker may have misled me and the scientific community

00:24:00.680 through the doctoring of images.

00:24:03.380 What she said to us today, Dr.

00:24:06.020 Schrag is very different.

00:24:07.600 She said to us in a statement we just got this morning, quote, I have absolute confidence

00:24:12.020 in the scientific accuracy of our A beta star 56 research.

00:24:18.560 Despite recent media reports focused on images included in a research paper from 2006, while

00:24:24.880 the editing of select images should not have occurred, the adjustments are non-material,

00:24:31.120 inconsequential, and have no bearing on the research findings themselves.

00:24:36.560 Your reaction to that?

00:24:39.440 Well, I think that I would encourage them to cooperate with the regulators and not only the

00:24:45.780 regulators, but also with the scientific community.

00:24:48.020 They say that daylight is the best disinfectant.

00:24:51.040 And I think sharing those images with the wider scientific community so that our confidence

00:24:56.500 can be improved would really help us to understand exactly what happened.

00:25:02.260 I will say there was quite a number of papers that were implicated in this.

00:25:07.800 And one of them, prior to the article that broke this news, they issued a correction for it, an

00:25:15.240 article in a prominent journal called Brain.

00:25:17.840 And then they said the same thing, that the changes should not have occurred.

00:25:22.260 They were inappropriate changes to those images, but they didn't change the results at all.

00:25:26.660 And when I analyzed the new images that they released, I found quite the opposite.

00:25:30.960 It looked to me like quite a number of the results were very substantially different with the new

00:25:38.180 unadjusted images that they released.

00:25:40.780 And so I think I certainly accept that Dr.

00:25:44.780 Ash believes the results of these studies, but I think without sharing the results, we're

00:25:50.000 just not going to have confidence in them.

00:25:51.900 I think that they should make the original material available for closer scrutiny.

00:25:56.480 She does not seem to be even trying to push back on the fact that the images were manipulated.

00:26:03.820 I mean, she says that in her study, I mean, in her statement.

00:26:06.900 But to say that the, quote, adjustments are non-material, inconsequential, and have no bearing

00:26:12.580 on the research findings is a different leap.

00:26:15.980 I mean, inconsequential, really?

00:26:18.360 Are they?

00:26:18.860 Quite simply, one has to ask, why were they done?

00:26:21.480 You know, I don't think that if, you know, the fact that they were done speaks for themselves.

00:26:28.140 If they were inappropriately manipulated, then the data is simply not trustworthy.

00:26:32.720 And despite her opinion, which she's, of course, very much entitled to, if the images were

00:26:38.880 manipulated, the article must be retracted.

00:26:42.460 What does this mean?

00:26:43.360 And it hasn't been yet, correct?

00:26:45.720 Yeah, I think, of course, they're entitled to due process.

00:26:49.880 And again, as I said, the material we have access to is much smaller than, you know, the

00:26:56.220 whole sum of the data.

00:26:57.500 And so I understand these processes take time, and they must be fair.

00:27:01.820 What does this mean for, you know, scientific research when it comes to Alzheimer's causes

00:27:07.560 for the past, you know, since 2006?

00:27:10.520 Yeah, well, so as I mentioned earlier, there are other studies in this vein from totally

00:27:16.780 independent researchers.

00:27:17.920 So this is not the only foundation of the oligomer hypothesis, but it's an important piece of

00:27:24.180 it.

00:27:24.700 And I think that it has to be factored into the way we interpret all of the failed clinical

00:27:30.360 trials that have been targeting beta amyloid and different versions of beta amyloid, that

00:27:36.060 there are problems with the data, and the clinical trials are consistently showing us that this

00:27:42.760 approach has not been successful.

00:27:45.000 It is certainly appropriate to look at this pathway very, very carefully.

00:27:49.760 But I think the field as a whole needs to invest in alternative ideas.

00:27:55.660 Yeah, we started off the discussion by talking about two drugs that got FDA approval that a bunch

00:28:00.960 of Alzheimer's researchers like yourself said, what are we doing?

00:28:03.500 These cause more harm than good, and they're not actually helping patients.

00:28:07.780 And now we can sort of see how we got so far down this lane.

00:28:12.940 You know, studies like this one that have red flags all over them that form the basis for

00:28:18.820 development of drugs that have red flags all over them.

00:28:24.640 And here we are 16 years later without a cure and maybe having wasted a bunch of time and money.

00:28:31.200 Yeah, well, semifilum is not FDA approved yet, but it has been greenlit for clinical trials.

00:28:37.500 And I think it is just so critical that when we ask patients to take the risk of participating

00:28:43.040 in an experiment where we don't completely understand the risks and benefits, we owe them

00:28:47.820 the highest degree of candor and the highest degree of scientific integrity for the beginning

00:28:54.380 data.

00:28:54.780 We have an important ethical partnership with patients as physicians and scientists.

00:29:01.960 And we have to be able to say, you know, when there are problems, we have to be able to

00:29:07.720 say that out loud.

00:29:10.100 What kind of pushback, if any, have you gotten, Dr. Schrag, for doing all of this?

00:29:14.640 Well, I think that the field as a whole seems to be willing to consider these concerns.

00:29:22.640 You know, I think that we're at a moment where we have the backdrop of a lot of failed clinical

00:29:27.360 trials, and there's a lot of introspection at this moment.

00:29:29.800 And I think that's been helpful, that many of my colleagues are willing to candidly look

00:29:35.960 at this, most of them.

00:29:37.720 And even people who are firmly in the camp believing that amyloid is a major driver of

00:29:43.680 the disease have been willing to candidly look at these concerns, and I've been impressed

00:29:47.900 and encouraged by that.

00:29:49.880 Do you worry at all about, you know, the NIH controls everything?

00:29:52.820 It controls funding to basically every university, every scientist.

00:29:56.680 And so far, all they're saying is, credible complaints will go to the Department of Health

00:30:01.800 and Human Services Office of Research Integrity for review.

00:30:04.260 So that agency could then instruct grantee universities to investigate prior to.

00:30:09.700 In other words, it's going to take years.

00:30:12.180 They say, if it's deemed credible, we'll investigate.

00:30:14.860 But we may make the university investigate first, which could take years and might not become

00:30:18.540 public unless it results in an official misconduct finding.

00:30:22.600 To me, it just seems like push it, push it down the road.

00:30:25.480 And the NIH could control your future as a researcher in the grants and so on you get.

00:30:30.360 Well, I think the NIH certainly follows their procedures, but this is part of why it's so

00:30:37.240 important to have this conversation in the light of day with all of the stakeholders.

00:30:43.380 You know, when things reach a certain magnitude and patients are being exposed to drugs, they

00:30:49.120 deserve to have all of the facts.

00:30:51.580 And I absolutely appreciate that the NIH has to conduct a complete and full investigation

00:30:56.260 and that that takes time.

00:30:58.780 But patients are being exposed to these things today.

00:31:02.760 And I think that's why we have to be able to speak candidly about these issues.

00:31:09.140 The Science Magazine article, which broke this, and we're going to have the journalist

00:31:14.220 on next, has a great quote from you that reads as follows.

00:31:17.780 You can cheat to get a paper.

00:31:19.520 You can cheat to get a degree.

00:31:21.060 You can cheat to get a grant.

00:31:22.600 You can't cheat to cure a disease.

00:31:26.480 Biology doesn't care. 0.98

00:31:29.340 16 years post the publication of that paper, has biology told us not to believe it?

00:31:38.060 I think so.

00:31:39.280 I think a lot of my colleagues have reached out both before and after this became public

00:31:44.400 to say that they could not reproduce that data.

00:31:47.060 And that is the ultimate test.

00:31:48.420 So I think that we're learning and in any complex human endeavor, there's going to be some margin

00:31:55.500 of error.

00:31:56.160 And in science, we try very hard to correct it.

00:31:58.540 And frankly, there's going to be some margin of mischief in any complex human endeavor.

00:32:03.400 It doesn't mean the system is broken.

00:32:05.100 It means we need to be able to speak candidly and get back on track as soon as possible to

00:32:10.660 limit the damage.

00:32:12.640 Right on.

00:32:13.440 Right on.

00:32:14.140 Dr. Schrag, thank you.

00:32:15.360 So great to have you here.

00:32:16.580 I really appreciate all of it.

00:32:17.700 It's my pleasure to be with you.

00:32:20.620 All right.

00:32:20.800 We're going to be right back with one of the journalists who broke this story, what

00:32:24.780 he found when he had other doctors look into Dr. Schrag's discovery and what the NIH is

00:32:33.280 actually going to do about this.

00:32:35.180 Welcome back to The Megyn Kelly Show.

00:32:42.280 I'm joined now by Charles Piller.

00:32:44.060 He's an investigative journalist for Science Magazine, and he is the reporter to whom Dr.

00:32:49.040 Schrag turned when he knew he needed to get this information out to the public.

00:32:54.100 Charles, thanks so much for being here.

00:32:56.240 Thank you, Megyn.

00:32:57.720 So, I mean, what a story.

00:33:00.140 I have to say, my brother-in-law, Ken, brought it to me.

00:33:03.500 He was at our house and it just.

00:33:05.180 Blown in.

00:33:06.580 When this broke, he said, have you seen this?

00:33:09.140 And I said, what are you talking about?

00:33:10.380 No, this is crazy.

00:33:11.260 That's crazy talk, what you're saying.

00:33:12.900 He's like, no, read the whole thing.

00:33:14.160 And that's that day I sent it to my team saying, let's get these guys on.

00:33:17.040 This is incredible.

00:33:18.020 So great work to you.

00:33:19.560 And I'm sure your jaw dropped when you when you first spoke to Dr. Schrag, but you spent

00:33:25.440 months trying to make sure Dr. Schrag had it right.

00:33:29.840 Talk to us just a little bit about your investigatory process to make sure you didn't go too far out

00:33:34.840 on a limb that wasn't stable.

00:33:38.260 Sure.

00:33:39.060 And thank you so much for your comments, Megyn.

00:33:41.420 And so I handled this story as I would any of my investigations, which is to say that

00:33:48.560 one must validate the claims of a whistleblower.

00:33:51.320 And in this case, it required a very high degree of validation because the claims were so important

00:33:59.240 to the field of Alzheimer's research involving, as you said in the earlier segment, a seminal

00:34:05.100 paper that has had a lot of influence in the field.

00:34:08.620 And so the way I went about it is that I wanted to investigate the veracity of his concerns

00:34:16.040 based on his analysis of actually turned out to be well over 170 images in two categories.

00:34:24.880 One involving the Cassava Sciences experiments and related experiments from scientists who

00:34:32.240 are affiliated with that company in some way.

00:34:34.860 And the other involving Sylvain Lesney and Karen Ash's work and independent work by Sylvain

00:34:40.840 Lesney.

00:34:41.360 And so what I did is I wanted to look at two categories of validation.

00:34:46.880 One is image forensic analysts who are experts in understanding how these images could possibly

00:34:55.040 be doctored and how that might have been done.

00:34:58.180 And the second category were experts in the field of Alzheimer's research.

00:35:02.740 And in that latter category, I really wanted to make sure that I was not just going to critics

00:35:09.100 of the amyloid hypothesis.

00:35:10.500 I wanted to go to a range of people who understood the technology well, understood the science deeply,

00:35:18.020 and would have no reason to be critical or supportive one way or the other.

00:35:25.660 And I was able to give each of these scientists and forensic analysts the full Schrag dossiers on 0.88

00:35:34.860 both the Simufilum case and also the Lesney work.

00:35:39.180 And what I found is that every single scientist who evaluated these images and the forensic image

00:35:47.820 analysts all agreed that his work was credible.

00:35:50.880 It was well supported.

00:35:52.380 And it suggested the possibility of misconduct or at the very least, terrible errors.

00:35:59.840 And just to take a step back, you know, in terms of how it got to you and in your lab in the

00:36:07.860 first place, the good doctor was very smart because he understood as a whistleblower,

00:36:12.580 he needed to bring this to the NIH.

00:36:14.580 But he well understood how slow those wheels of justice could move.

00:36:19.540 And so tell us what else he did.

00:36:22.380 Sure.

00:36:22.860 So I had been talking with Matthew Schrag beginning in December of last year, and this was a point

00:36:32.380 at which he was largely through with the analytic work that he had done on the cassava sciences issues.

00:36:41.380 But he was, as any, I think, expert would be doing, trying to refine his skills further.

00:36:48.160 And in so doing, he stumbled on, you might say, the Lesney issues, the issues related to

00:36:56.000 this very important amyloid beta protein that was dubbed Star 56 by Sylvain Lesney and Karen

00:37:04.080 Ash.

00:37:05.000 And it was really around the time I started talking to Schrag that he started to see this

00:37:12.320 happening with Lesney.

00:37:14.040 And I was talking with him, and I remember quite distinctly, as he started to describe

00:37:20.120 it to me, in a sense, both of our jaws dropped at that moment.

00:37:25.320 We both realized that this was something of some great significance, in some ways, much

00:37:32.100 more important scientifically than the cassava sciences issues because of the wide influence

00:37:40.620 that the Sylvain Lesney and Karen Ash study had had, and their other work in the same

00:37:46.700 realm.

00:37:47.780 So he came to me for a couple of reasons.

00:37:51.340 One is that, as you say, he wanted to see it get a wider audience.

00:37:55.280 He also wanted to work through a venue that would have the scientific backdrop and expertise

00:38:03.760 to do a close examination of this.

00:38:07.260 Science Magazine, of course, is a scholarly journal, but also our journalistic portion

00:38:13.420 of the magazine.

00:38:15.160 You know, we have access to a lot of good expertise and a lot of ability to delve deeply into these

00:38:21.800 kinds of technical matters.

00:38:23.580 Yeah.

00:38:23.760 With all due respect to People, there's a reason he didn't go to People Magazine.

00:38:27.120 I mean, he wanted somebody who could really fact check him and not just rubber stamp what

00:38:33.620 he was saying.

00:38:34.380 He seems like a true seeker of truth.

00:38:37.700 So he comes to you, he went to the NIH, and it sounds to me like the NIH is not doing much

00:38:43.880 so far.

00:38:44.440 Am I correct about that, Charles?

00:38:46.000 It seems like it's basically saying, we'll take a look at it if we deem this complaint

00:38:51.880 credible.

00:38:52.320 Yeah, I mean, I think the NIH is pretty opaque about what they do.

00:38:58.640 I think we can read the tea leaves.

00:39:01.680 It looks like they referred it to something called the Office of Research Integrity, which

00:39:06.640 is part of the Health and Human Services Department, kind of a sister agency to NIH.

00:39:11.680 This is a pretty small outfit within the federal government that takes another look at it.

00:39:17.320 So what you're talking about is an initial look, and then a second look by a second federal

00:39:22.680 agency.

00:39:23.700 And then if they deem the concerns raised by Schrag to be potentially credible, then they

00:39:30.760 might refer it to the University of Minnesota in this case, where Sylvain Lesney and Karen

00:39:36.120 Ash work.

00:39:36.780 And it appears that that's what happened, but we don't know for sure, that we do know

00:39:41.860 that the University of Minnesota is doing their own close look at this, or so they say.

00:39:47.920 What about Dr. Lesney?

00:39:49.520 Where is he?

00:39:51.280 Well, so in the course of my reporting, naturally, I made very, very serious and repeated efforts

00:39:59.640 to engage Dr. Lesney, his voice would have been critical to understand the significance

00:40:07.120 of what we were looking at in the Schrag dossier associated with his work, and also with the

00:40:13.420 additional reporting that I had done.

00:40:15.680 And unfortunately, he did not agree to talk with me, nor did Professor Ash agree to talk

00:40:23.400 with me, although she did email me a cryptic statement before the story ran.

00:40:27.460 I think that the issue with approaching these scientists, to me, was one of me being as

00:40:38.480 straightforward and complete as I could in helping them understand what I was up to, what

00:40:45.420 I was seeing, what I was finding, and why their view on it would be so critical to give

00:40:51.980 the fuller picture to our readers.

00:40:53.840 And consequently, I emailed them not just the full dossier created by Matt Schrag, but

00:41:02.760 I also sent them a detailed list of questions so that there were no surprises.

00:41:07.140 They knew exactly what I had from the very beginning.

00:41:10.820 She originally told you she found your reporting sobering, right?

00:41:16.440 Then she says to NBC, she wants the study to be retracted in its entirety, saying this is

00:41:23.400 devastating to discover that a coworker may have misled me and the scientific community

00:41:27.740 through the doctoring of images.

00:41:29.580 Then to us today, I have absolute confidence in the scientific accuracy of our A-beta star

00:41:36.280 56 research, despite recent media reports focused on images included in this research paper from

00:41:41.380 06. While the editing of select images should not have occurred, so she's not disputing that

00:41:47.000 they were manipulated, the adjustments are non-material, inconsequential, and have no bearing

00:41:52.760 on the research findings themselves.

00:41:55.240 She's having quite an evolution.

00:41:56.620 I mean, you and I know as journalists, she's having quite an evolution on her response.

00:42:01.020 Sobering, pull the study, devastating to absolute confidence, non-material, inconsequential,

00:42:09.000 no bearing on my research, what do you make of it?

00:42:12.600 Well, I think I would just go back and say, just as I felt that I needed to be skeptical

00:42:18.680 of Dr. Schrag's work in order to validate it so that it had more credibility for our readers,

00:42:26.000 I would just kind of apply the same kind of skepticism to Dr. Ashton's comments.

00:42:33.700 Let me just say that in her comments to you and others, she has tried to minimize the influence

00:42:40.860 of these changes, these apparently improper changes to images in her work.

00:42:46.220 And it's not just this one study.

00:42:48.560 It's five studies that she did with Lesney and another 15 or 16 studies that Lesney did

00:42:57.900 independent of Ash.

00:42:59.180 And so consequently, we're talking about paper after paper, image after image, 10 total papers

00:43:06.780 involving this very important so-called A-beta star 56 protein that is at the heart of their

00:43:17.380 understanding of what might be a cause and effect relationship for Alzheimer's disease.

00:43:21.940 So what I guess I would say to that is, if she's so confident, then let's see the full

00:43:30.240 complete record of these experiments, put it in the hands of people who know how to evaluate

00:43:34.320 it.

00:43:35.080 And I guess perhaps at this point, it would be important to say that I have asked, and I think

00:43:44.100 a lot of experts in research review have raised the question about whether the university where

00:43:50.040 Ash and Lesney work is the appropriate institution to actually do this full and complete review.

00:43:56.640 I mean, let's face it, their employer has the least to win and the most to lose from doing

00:44:05.100 a thorough investigation that actually finds fault with the work being done in their own

00:44:09.200 labs.

00:44:09.980 So I guess I would just say I would find that suspect.

00:44:13.460 I think it would be important to have an independent kind of set of eyes that go over that work and

00:44:19.620 try to assess whether her claims associated with that research hold any water.

00:44:26.460 The way I see it, just to sort of, you know, dumb it down, is the amyloid hypothesis, you

00:44:32.340 know, that there's this sort of protein that these plaques cause Alzheimer's was one possibility

00:44:37.140 that scientists have been considering for many years.

00:44:39.540 But there are other lanes of possibilities.

00:44:42.080 And so let's say the amyloid hypothesis is like an apple. 0.98

00:44:45.280 Some people say an apple.

00:44:46.680 Apples cause Alzheimer's.

00:44:48.640 But other lanes are saying, no, it's oranges.

00:44:50.540 And other lanes are saying, no, it's plums.

00:44:52.520 And her team was like, it's definitely apples.

00:44:55.700 And not only is it apples, it's green apples.

00:44:57.940 We're advancing it even more.

00:44:59.220 We know specifically what kind of apple is causing it.

00:45:03.340 And then he put, Lesney put up photos showing the green apple doing damage.

00:45:07.520 And everybody said, oh, there it is.

00:45:09.740 We've got it.

00:45:10.340 This is the closest we've had to like proof of causation.

00:45:13.300 It's the green apple.

00:45:14.620 And now she seems to be sitting back saying, okay, he may have manipulated the photos.

00:45:19.940 I get it.

00:45:20.780 But I still have a bunch of rats who ate green apple, who were fine the day before and the

00:45:27.460 day after had serious memory problems.

00:45:29.500 So I'm good.

00:45:30.660 I don't really care what Lesney did with his little photos of my apples.

00:45:34.200 I saw the rats.

00:45:35.620 I knew that they had clean brains that could find the treats on day one.

00:45:40.880 I fed them the green apples.

00:45:42.580 And then day after that, they had memory problems.

00:45:45.140 Like, why isn't that an okay defense?

00:45:48.740 Well, let me put it in these terms.

00:45:51.200 So if you're a reasonable person trying to understand the truthfulness and the believability of a complex scientific experiment,

00:46:02.600 wouldn't it be good to take a comprehensive look at the entire body of work in order to understand it better?

00:46:08.760 So let me start with this 2006 study.

00:46:12.380 So in her comments to other media, Dr. Ash has said that it was only an image or two that were potentially altered by Lesney.

00:46:24.220 And actually, if you look at Schrag's body of work associated with that paper, it's six or seven images.

00:46:30.740 So, first of all, you're seeing a situation in which she appears to be minimizing the extent of the apparent problem.

00:46:38.160 Second, if you have a study where six or seven of the most important representations of data in the study are deeply suspect,

00:46:49.340 and I don't think there's much dispute that they are deeply suspect,

00:46:53.560 are you going to believe that they have no effect?

00:46:57.240 I think any reasonable person would at least ask the question, we can't just take our word for it.

00:47:02.800 We need to have this looked at much more carefully by a wider range of experts who have the knowledge,

00:47:08.720 the expertise, and the empowerment to do a closer look.

00:47:14.700 What's crazy in this story, among other things, and we have a lot more to get to,

00:47:18.560 is what happened to Lesney after Dr. Schrag blew the whistle and the money that he's been getting.

00:47:26.180 So, he may have gone underground in terms of the press, but he's still out there,

00:47:30.080 and we're going to pick it up there right after this very quick break.

00:47:33.240 Don't go away. Charles is staying with us.

00:47:35.140 And remember, folks, you can find The Megyn Kelly Show live on Sirius XM Triumph Channel 111

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00:47:51.720 or wherever you get your podcasts for free.

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00:48:03.260 So, Charles, one of the things that you did was to find out, go to other experts and say,

00:48:08.420 take a look at Dr. Schrag's conclusions about the images in this paper.

00:48:13.360 And you went to some real experts in the field.

00:48:16.260 What did they say?

00:48:16.840 Well, basically, each one of them agreed that the concerns raised by Dr. Schrag were credible.

00:48:25.700 They were well supported by his work and raised serious questions about the validity of an entire

00:48:33.580 body of research associated with Dr. Lesney, including this, as you mentioned, seminal paper,

00:48:40.120 as well as others associated with this protein they found that seemed to suggest a cause and effect

00:48:46.740 relationship with a kind of dementia associated with Alzheimer's.

00:48:51.480 This is from your article, because you did a six-month investigation prior to publishing this.

00:48:56.780 A leading independent image analyst and several top Alzheimer's researchers, including George Perry of the

00:49:02.240 University of Texas, San Antonio, John Forsyth of the University of California, San Francisco, reviewed most of Schrag's findings.

00:49:08.760 They concurred with his overall conclusions, which cast out on hundreds of images, including more than 70 in Lesney's papers.

00:49:15.180 Some look like shockingly blatant examples of image tampering, says Donna Wilcox, an Alzheimer's expert at the University of Kentucky.

00:49:23.400 The authors, quote,

00:49:24.100 Let's talk about why this hypothesis was out there

00:49:50.540 and being researched to begin with, because I know that one of the things I found interesting about your paper

00:49:57.180 was back to my apple, orange, pear, plum, whatever my third fruit was.

00:50:05.280 Example, there are other lanes of study as the cause of Alzheimer's.

00:50:12.480 And one of the things you talked about was these other lanes have been sidelined.

00:50:15.980 They've been effectively sidelined for a long time now because we've been so focused on the apple and the green apple.

00:50:23.100 In other words, this amyloid hypothesis. 0.97

00:50:27.500 Yes, let me put it a little bit into the context of what was happening at that time.

00:50:32.920 So in 2006, we had already begun to see failure after failure after failure of drugs targeting amyloid proteins.

00:50:42.020 Failure in the sense that they did not seem to improve cognition, nor did they seem to prevent the disease.

00:50:49.500 Consequently, that idea, the so-called amyloid hypothesis, was under some strain.

00:50:55.540 Some skepticism was increasing.

00:50:57.900 And then this important study entered the breach.

00:51:02.460 This was the 2006 study in Nature, which, as many listeners may know, is one of the most important scientific journals.

00:51:10.420 And this study by Lesney and Ash seemed to show a cause and effect relationship showing neurocognitive impacts, memory problems in rats associated with their star 56 protein.

00:51:27.800 And so for the first time, there was a substance that seemed to directly cause effects in an animal that mimicked Alzheimer's disease and gave a lot of credence and hope to people who had been believing all along that this discovery would be made and that the amyloid hypothesis would be proved out in a very practical way that would present new targets for drugs that would be able to cure the disease eventually.

00:51:57.800 So that was the contribution it made.

00:52:00.220 It made a contribution of great importance to the field at a moment when the amyloid hypothesis was meeting with more skepticism.

00:52:09.920 Yeah, the people were starting to get a little wobbly on whether they had it right.

00:52:14.100 And then along comes, boom, this 2006 study, this gift shoring up their lane.

00:52:19.220 This is from your article.

00:52:20.740 Scientists who advance other potential Alzheimer's causes, such as immune dysfunction or inflammation, complain they've been sidelined by the amyloid mafia. 0.99

00:52:34.640 Forsyth, the doctor I mentioned a second ago, says the amyloid, I mean, hypothesis became the scientific equivalent of basically the model of the solar system in which the sun and planets rotate around the earth.

00:52:48.100 And people had started wondering by 2006 whether the field needed a reset.

00:52:53.720 No worries.

00:52:54.820 Enter Dr. Karen Ashe with her trusty protege, this French guy who come out with this study. 0.65

00:53:02.820 And what do we know about this French guy, Dr.

00:53:05.320 Lisney?

00:53:05.660 Because like he's not speaking and he's his fingerprints are all over this and many other studies.

00:53:12.440 But he's still an associate professor at the University of Minnesota.

00:53:15.980 I mean, how underground can he go?

00:53:19.120 Well, so, yes, I think in fairness to Lesney, he does deserve an opportunity to defend his work during an investigation being conducted by the university.

00:53:29.380 I hope that will be a rapid and thorough investigation.

00:53:33.380 My fear, and I think it's supported by the experience of many other investigations by universities and other entities with vested interests in a particular outcome, is that it won't be thorough and fast.

00:53:46.320 But I think we need to hold out the possibility that the university will get to the bottom of this.

00:53:52.720 So I think Lesney deserves his opportunity to defend himself, and I presume he is doing so in the university's look.

00:54:01.080 But let's take it a step back to the evolution of Lesney himself as a scientist.

00:54:07.480 So I was very curious about this idea that he was the guy who was responsible for all this, as Karen Ash now seems to be implying, or in some cases, almost openly saying.

00:54:21.260 And I think what I wanted to do was to ask myself the question, how far back did these concerns with Lesney's work go?

00:54:30.520 And Matt Schrag had looked at papers that go back a couple of decades, and others, including Elizabeth Vick, who reviewed some of Lesney's even earlier work, found additional problems.

00:54:44.920 So we had more than 20 papers going back a couple of decades where it seemed that there were anomaly after anomaly, question after question.

00:54:55.360 And that sort of a history certainly does raise eyebrows.

00:55:00.180 But to me, the acid test was talking to one of his mentors at the University of Cannes in Normandy, France, where he did his PhD training.

00:55:09.740 And this particular professor, he said that he was doing a joint paper with Lesney back in his PhD days, 2002 approximately.

00:55:22.360 And he found images that Lesney had been producing in service of that paper that he regarded as suspect, untrustworthy.

00:55:32.180 He tried to have those images repeated by other graduate students.

00:55:36.660 They could not get the same result.

00:55:38.760 So finally, this professor pulled the paper, which was about to be published in a prestigious journal.

00:55:44.700 And he pulled it because he feared that would affect his own scientific integrity as the senior author of the paper.

00:55:50.880 So I guess what I'm saying is that there had been a history of suspicion, a history of concern.

00:55:58.180 And in the field, he became known as someone who had the ability to get things done in the lab that some others were not able to do.

00:56:08.400 He was a brilliant bench scientist, they call it, who was able to complete experiments in ways that others found very difficult to do or could not accomplish.

00:56:18.780 And when you have that combination of history of difficult to prove images that appear to have been doctored and suspicion from his own mentor in France,

00:56:32.380 and this idea that he had kind of the ability to get things done in the lab that others could not accomplish.

00:56:40.400 And then you have image after image and paper after paper that is suspect.

00:56:44.740 Well, that paints a picture of someone who, you know, maybe has been engaging in possible misconduct for a long time.

00:56:52.880 I think people have looked at this sort of activity in science or really in other fields is that it rarely occurs just once in one image.

00:57:00.560 It's usually a pattern.

00:57:02.020 No, if this is true, he loves to doctor images.

00:57:05.320 He's the Kim Kardashian of science.

00:57:07.620 I mean, he just loves he's got the same little perfect 365 app on his phone, except he's putting scientific data in there instead of noses and butts and legs.

00:57:18.500 Sorry, Charles, that's my level of trying to bring the story to the viewers.

00:57:21.920 But seriously, if this is true, this guy's got a massive problem and he's got a lot to answer for, but seems to be going the other way.

00:57:32.060 According to your piece, not only did he become the leader of the University of Minnesota's neuroscience graduate program prior to this.

00:57:39.880 This is two years ago, but he's leading their neuroscience graduate program.

00:57:43.920 It's a respected program, respected university.

00:57:46.200 If this guy did all this, that should end.

00:57:48.340 And tell us what happened in May 2022, four months after Dr. Schrag delivered his concerns to the NIH.

00:57:59.040 Yes, that is a kind of a befuddling aspect to this whole strange story.

00:58:05.840 And in May of this year, he received what is called an R01 grant.

00:58:12.060 So this is a prestigious, important grant from the university, very competitive to get these grants.

00:58:18.340 It can give him up to five years of funding for his work.

00:58:23.120 And this was, as you say, months after the agency knew that his work was under a cloud, that years and years of his studies were being suspected for possible manipulation and scientific misconduct.

00:58:38.460 So that's question number one about the NIH's action.

00:58:41.400 I would add that there's another strange twist to this NIH grant story, which is that the grant administrator for Dr. Lesney for his new grant is a guy by the name of Austin Yang, who is himself a respected scientist and was a co-author of the 2006 study in Nature, this very important influential study that is now under a cloud.

00:59:06.480 That that that is not OK. You know, these conflicts of interest are all over the place.

00:59:12.000 By the way, what what if any connection does Francis Collins at the NIH have to this story?

00:59:17.860 None whatsoever that I know of.

00:59:20.300 OK, just wondering, because his name obviously has been in the news so much.

00:59:23.320 What what what about that? Because, you know, there are a lot of people in the country who have a lot less faith in institutions like the NIH in the wake of all the covid madness than they used to.

00:59:34.620 And, you know, this is not going to help this.

00:59:37.820 This story is not going to help.

00:59:39.360 What are people to make of our lead medical institutions within the government and the faith that we should be placing in them?

00:59:47.480 Well, let me say that the NIH is so enormously important to our country, so enormously important to curing diseases and to understanding more fundamentally the nature of the bioscience behind many of the dread illnesses that that are being explored by physicians and scientists all over the world.

01:00:10.760 So I have nothing but praise for much of the work that IH does now as an investigative reporter, I have looked at federal agencies, including the Food and Drug Administration and the National Institutes of Health when there are possible lapses or concerns associated with how they administer their programs.

01:00:31.100 And so like any big bureaucracy, like any human endeavor, there's going to be questions.

01:00:37.140 There's going to be lapses in judgment at times.

01:00:39.960 There's going to be doubts.

01:00:41.660 There's going to be conflicts of interest.

01:00:43.840 And I think it doesn't invalidate the enormously important body of work that the agency has funded over the years, of course, including work in Alzheimer's disease.

01:00:54.220 But it does raise an interesting question about whether there should be a reexamination of how they prioritize this work, whether they became, in a sense, what some scientists might call captive to certain interests.

01:01:09.060 Because, again, it's been described as the amyloid mafia in this case.

01:01:13.100 I'm not saying that the amyloid hypothesis is useless or is somehow disproved.

01:01:19.920 What I'm saying is that when you have a situation where year after year, drug after drug has failed when targeting amyloid plaques, that it's worth asking, is the priority on that?

01:01:34.600 Where the enormous proportion of the amyloid hypothesis is focused directly on the amyloid hypothesis and on enormous billions of dollars of pharma company drug development efforts are focused on that.

01:01:51.020 It's worth asking the question, should there be a shift in priorities or at least a broadening of interest in this, especially in light of what we've seen with the Lesney-Ash situation, where some of the key research supporting that hypothesis has been found to be deeply suspect?

01:02:08.520 Well, I mean, and that's the thing. I mean, these poor families out there suffering with Alzheimer's now waiting for the next drug to come through the pipeline.

01:02:17.080 The disappointment of Adjahelm, you know, the drug we talked about earlier that did get FDA approval, but $57,000 a year, $56,000 a year flopped because there doesn't appear that it was doing what they had said it would do.

01:02:33.360 And then now we've got some euphilim who, you know, which we discussed with the doctor, very concerned about that one, too.

01:02:41.900 And I'm sure there's others that are being researched right now, maybe in part in the green apple lane, you know, maybe in part based on this research.

01:02:50.740 So what does this mean for families who are waiting for the breakthrough?

01:02:57.280 Well, I would say this is a terribly sad situation, according to experts with whom I've spoken, that really what we're talking about is opportunity costs.

01:03:06.640 So if you're focusing so much of your effort and so much of your money on a particular scientific direction that has failed over and over,

01:03:16.100 then to the neglect of other ideas that themselves could have some possible benefit and could be fruitful and leading to potential remedies for Alzheimer's disease,

01:03:29.520 I think the patients and their loved ones have reason to be concerned and have reason to be angry that this occurred and that these suspect studies have proved to be so influential.

01:03:42.620 Now, that said, I would say that to me, one of the acid tests for me was talking to a really eminent scientist by the name of Dennis Selko,

01:03:56.740 who's at Harvard University and is a progenitor of the amyloid hypothesis and someone who believes deeply in the importance of studying the amyloid oligomers that Dr. Schrag had mentioned in his segment.

01:04:12.620 That these are the subtype of amyloid proteins that are thought to be toxic and to be perhaps instrumental in Alzheimer's disease.

01:04:21.560 So Dr. Selko said to me that there are currently clinical trials of drugs that are attacking these oligomer types of amyloid proteins.

01:04:38.000 And if they fail, the amyloid hypothesis is under some duress.

01:04:42.800 Now, that was pretty interesting to me because this is a guy who is a total advocate for this hypothesis,

01:04:49.060 believes deeply in its importance, and has spent a lot of his career studying how best to get at it.

01:04:55.340 Yeah, the NIH spent about $1.6 billion on projects that mention amyloids in this fiscal year.

01:05:06.720 That's about half of its overall Alzheimer's funding.

01:05:10.160 So we'll see whether we'll see whether this shakes that or opens up funding in the other lanes and leads to a realistic reassessment of this paper and others like it,

01:05:22.460 in which this guy Lesney has had any connection.

01:05:26.000 Charles Piller, I hope you win all sorts of awards for this article.

01:05:29.120 It was brave and it was important, and I encourage the audience to read it because Charles actually does a great job of walking you through it.

01:05:35.960 You know, amyloid this and all. 0.72

01:05:37.200 It's complex, right?

01:05:38.460 But he takes the time to walk you through it in a way that makes sense.

01:05:41.260 All the best to you.

01:05:42.880 Thank you, Megan.

01:05:44.340 Up next, one of the experts on Alzheimer's, Dr. Dale Bredesen and what he thinks of what you just heard.

01:05:53.040 Don't go away.

01:05:59.120 Welcome back to the Megan Kelly Show.

01:06:01.840 My next guest is an expert in the field of brain health who has done some revolutionary work to treat Alzheimer's.

01:06:08.680 He also happened to be Dr. Karen Ashe's chief resident when she was an intern.

01:06:14.520 Dr. Dale Bredesen is a UCLA professor in the Department of Molecular and Medical Pharmacology and author of The End of Alzheimer's.

01:06:23.260 Great to have you back, Doc.

01:06:24.300 Thank you for being here.

01:06:25.140 So what did you make of this article in Science Magazine and of our whistleblower's testimonial?

01:06:33.020 Yeah, thank you very much, Megan.

01:06:35.060 And here's the problem.

01:06:36.540 This is actually part of a much bigger problem.

01:06:39.360 So we are all witnessing the Titanic, that is mainstream medicine, going down because it has rammed into the iceberg of chronic illnesses.

01:06:53.740 And I'm talking about Alzheimer's, Lou Gehrig's disease, frontotemporal dementia, Lewy body disease, on and on, CBD, PSP, all these other ones, and including late stage cancers, including chronic renal failure.

01:07:09.300 We are all in an era in which mainstream medicine is treating things the way we treated them in the 20th century, simple illnesses, viral illnesses, bacterial illnesses, things like that.

01:07:23.400 And so we're ending up with things where the big problem here is really about what Alzheimer's is.

01:07:30.240 And let me just for one moment say, yes, I've known Professor Ash for 40 years.

01:07:35.100 She is a brilliant scientist, a brilliant neurologist, and she's absolutely committed to finding the mechanisms underlying Alzheimer's disease.

01:07:45.960 And the work that she did, you did a beautiful job with Charles Piller and with Dr. Schragge, but didn't mention that this is based on an analogy with Nobel Prize winning work.

01:08:00.100 And this was from Professor Stan Prusner, that identified in the case of prion diseases, this is a different kind of neurodegenerative disease, looks a little like Alzheimer's, typically faster than Alzheimer's disease and much more rare.

01:08:15.820 And he found one form of a protein that is normal, and one form that's abnormal, and if you give the abnormal one, the person or the animal gets the disease.

01:08:27.820 So this was an analogy here, which I think is one of the reasons that it was, you know, interesting to people at the beginning.

01:08:34.520 Aha, we have the same story, makes sense.

01:08:37.580 But as you've shown beautifully, this is much more complex.

01:08:41.540 And I should add, you mentioned the green apples.

01:08:45.820 In this case, this is a brew, this stuff, this stuff interchanges.

01:08:50.180 So you have green apples, red apples, and yellow apples, and they're changing into each other.

01:08:54.900 You have larger apples, smaller apples, you have apples that are sticking to each other, just like heated gummy bears.

01:09:00.860 So you've got this brew, and it's not simple.

01:09:04.640 And they're trying to say, is there one part of this brew that is actually causing the disease?

01:09:10.940 And you mentioned Professor Selko, who was really the first, many, many years ago, to argue that it was assemblies of small numbers of these amyloid molecules that were the critical players.

01:09:24.880 But here's the problem.

01:09:26.420 That doesn't explain the disease.

01:09:28.580 And as Charles mentioned, the problem is that when you remove the amyloid, you don't get better. 0.74

01:09:35.100 So we're left with this amazing paradox for lots of reasons.

01:09:40.200 Amyloid looks like a bad actor.

01:09:42.420 There it is, sitting there in the brains of patients with Alzheimer's.

01:09:46.260 There it is.

01:09:47.040 When you look and you see this stuff, you now drop it into cell culture, or you mentioned into Professor Ash's mouse brains.

01:09:55.680 And absolutely, you get symptoms.

01:09:58.040 There's no question.

01:09:59.300 Multiple forms of amyloid are toxic.

01:10:02.520 But the paradox is, when you now remove them with antibodies, and Aduhelm was not the first.

01:10:11.280 Bapunuzumab failed.

01:10:12.740 Solonazumab failed.

01:10:14.200 Crenazumab.

01:10:14.780 Gantanarumab.

01:10:15.420 Just go right down the list.

01:10:17.220 They have all failed.

01:10:19.300 And so people keep saying, well, it's because of this.

01:10:21.720 Well, it's because of that.

01:10:22.460 Yes.

01:10:22.840 When you put $40 billion into developing these things and trialing them, it's hard to say, you know, this has really failed.

01:10:30.240 But the surprise was that the FDA actually approved this, when in fact, the trial proved just the opposite of what the reason that they approved this.

01:10:42.080 They approved it because they said, well, it removes amyloid.

01:10:45.100 So we expect it to have clinical benefit.

01:10:47.920 No, that's exactly what all of these trials showed is not the case.

01:10:52.100 When you remove the amyloid, it does not give you clinical benefit.

01:10:56.700 So we're left with we need a better understanding of this disease.

01:11:01.940 It just it's so undermining of my own faith in places like the FDA, not to mention movies like Dope Sick.

01:11:08.020 But there are all sorts of reasons to be skeptical of them and whether they're acting in our best interest.

01:11:13.340 Let's not even get started on covid and the vaccine and so on.

01:11:17.540 I just think people see this sort of this rubber stamping of drugs that really might be hurting the sickest and most suffering amongst us.

01:11:25.120 And we think, forget these guys.

01:11:27.120 We can't trust the FDA.

01:11:28.440 Can't trust the NIH.

01:11:29.460 Why are they giving this Dr. Lesney more money after this well credentialed whistleblower went to them and said, here are all the images.

01:11:38.180 This guy appears to have been doctoring, manipulating, editing to use his boss's word, images in study after study.

01:11:46.960 And they still give him money.

01:11:49.320 It's a good point.

01:11:50.380 You know, we're right back to cold fusion, aren't we?

01:11:52.980 This is cold fusion in the brain.

01:11:54.920 You know, does it work?

01:11:55.820 Does it not work?

01:11:56.600 Is this what's going on?

01:11:57.640 And you really can't put the toothpaste back in the tube.

01:12:01.180 Once you've given out millions and millions of dollars of grants for what is now a suspect result, are you going to ask for that the grants be returned?

01:12:10.640 What are you going to do now?

01:12:12.860 In this case, again, this is there's some important nuances here.

01:12:17.060 It may turn out, just as Professor Ash has suggested to you, it sounds like today, that this will all turn out to be supportive of her theory and supportive of the work they originally published, even though there are clear red flags about how this was presented.

01:12:34.040 Or it may turn out, or it may turn out not to be the case.

01:12:37.000 And so you're right, this is really concerning.

01:12:40.300 And I think it just shows how complicated and how difficult research into human conditions is.

01:12:47.960 And the fact that humans are complicated organisms.

01:12:51.680 And there's a lot going on here, far more than just amyloid.

01:12:56.680 Multiple amyloid species clearly have toxic effects.

01:13:00.800 But the question is, is that the cause of Alzheimer's?

01:13:04.400 It is likely to be a mediator, but not the upstream cause of what's going wrong in an Alzheimer's brain.

01:13:12.400 And what do you think is the cause?

01:13:15.020 Talked about this a little bit the last time you were on.

01:13:17.400 Yeah, we did.

01:13:18.180 And actually, you know, we've had a tremendous amount of pushback and people just saying, you know, this can't be.

01:13:23.720 So what we're arguing is this.

01:13:26.160 And I'm glad you asked.

01:13:27.160 Thank you for asking that question.

01:13:28.800 So here's the thing.

01:13:30.100 There are lots of theories of Alzheimer's, as you know.

01:13:32.800 It's herpes simplex.

01:13:34.080 It's prions.

01:13:35.040 It's amyloid.

01:13:35.960 It's tau.

01:13:36.680 It's type 3 diabetes.

01:13:38.820 It's on and on and on.

01:13:40.460 You know, it's reactive oxygen species, free radicals, all these ideas.

01:13:44.980 None of them has led to a successful treatment.

01:13:48.960 So what our research over the last 30 years has suggested is that this is fundamentally a different type of disease.

01:13:57.240 It's not a simple it's amyloid or it's tau or it's something like that.

01:14:01.580 This is a network insufficiency.

01:14:04.540 So if when you change, it really changes the way you think about this illness.

01:14:09.840 And it fits much better with all the data.

01:14:13.180 So the idea here is you have this beautiful plasticity in your brain.

01:14:17.640 You're learning all sorts of wonderful things.

01:14:19.540 You're remembering all sorts of wonderful things.

01:14:21.980 You can make new synapses.

01:14:23.500 You can support them and so forth and so on.

01:14:25.980 And in fact, the big issue with Alzheimer's, as you know, is the loss of those synapses.

01:14:30.440 So what our research suggested, and we've just published a successful clinical trial based on the implications of this, is that you have this is a network.

01:14:39.780 This is just like running a large company or running a country.

01:14:43.880 There are many, many different contributors.

01:14:46.780 And in the case of Alzheimer's, we initially identified 36 different contributors.

01:14:52.740 There are a few more.

01:14:54.040 But the good news is it's not thousands.

01:14:56.820 There are dozens.

01:14:58.100 And so insulin resistance is critical.

01:15:01.200 Ongoing inflammation, various pathogens, various toxins.

01:15:05.920 All of these things can change that network function.

01:15:10.980 And so the idea of just doing the same thing for each person, it's like taking every single car that comes into a garage not doing well and just filling it up with gas.

01:15:21.820 Yeah, a couple of the cars, that's going to be fine.

01:15:24.160 But you need ultimately to treat these cars as complex mechanics and look at what's going on.

01:15:33.480 And the same thing needs to be done for people with Alzheimer's, and it is not being done in mainstream medicine.

01:15:39.600 We need to look at many, many different contributors.

01:15:43.360 We need to have computer-based algorithms that will now look at these data and say, okay, in this particular person, it was mainly A, B, C, D, E.

01:15:52.120 In this person, it was mainly F, G, H, I, J, et cetera.

01:15:55.420 Well, let me ask you a question about that, because I'm just looking at the specific factors got my brain moving.

01:15:59.900 So you could have a person who came in to see you who says, very outgoing, extroverted person who says, I've got tons of friends.

01:16:08.760 I love to smoke and drink with them many nights a week.

01:16:12.200 I know I shouldn't, but I do.

01:16:14.020 And I've got high cholesterol, and I've got some inflammation, and I know it's not great, but I think I have some memory issues.

01:16:23.260 That's patient A.

01:16:24.400 Patient B comes to you and says, I'm an introvert.

01:16:27.320 I exercise every day.

01:16:29.240 I do it in my house by myself.

01:16:31.920 I have a very, very stressful job, but I eat very well, but I don't like to see people.

01:16:39.200 And I'm having some memory issues, and I'm worried that I have dementia.

01:16:42.880 You actually would treat them differently.

01:16:45.620 You would see different problems that lead to dementia in each one of those patients.

01:16:50.760 Absolutely.

01:16:51.500 We right now look at 150 different variables.

01:16:54.480 So we're looking at, is this person insulin resistant?

01:16:58.060 Do they have ongoing inflammation?

01:17:00.620 Do they have different types of pathogens?

01:17:03.540 Do they have a leaky gut? 0.77

01:17:05.280 All of these things.

01:17:06.340 Isn't it amazing, though, Megan, when they have all of these theories, each one has a little bit of supportive evidence.

01:17:13.580 Now, if this were something simple, one theory would have all the evidence, and all the others would have none.

01:17:18.380 Yeah, just stop smoking.

01:17:19.700 You're good.

01:17:21.280 That's not the case.

01:17:21.900 But some of the factors that did jump out at me were, it's not great.

01:17:25.240 Smoking, of course, is not great.

01:17:26.400 Smoking is bad for everything.

01:17:28.260 Smoking is not great.

01:17:29.540 High cholesterol, not great.

01:17:31.560 No socialization, low socialization, not great.

01:17:34.420 No exercise, not great.

01:17:37.360 A balance that doesn't have enough folate in it.

01:17:39.700 I saw you tweeting about that recently.

01:17:41.080 You know, the guy got some spinach in there and some kale and so on.

01:17:44.480 So there are all sorts of different things that one person might be doing that could be bad for them.

01:17:49.600 And somebody else might think that they're doing just fine because they're eating well and they're not drinking and they're not smoking.

01:17:54.080 But they're not getting enough social interaction, which apparently is also not so great.

01:18:00.020 And leaky gut. 0.92

01:18:01.600 I mean, now in the past few years, we've been talking about the microbiome and taking a probiotic.

01:18:06.760 But like, how the hell do you know if you have a leaky gut and why should we be worried it's going to cause Alzheimer's?

01:18:11.820 This is a great point.

01:18:13.920 And we need to have more doctors understand this very point that you need to know if someone has a leaky gut.

01:18:20.640 You need to know, by the way, not only about their gut microbiome, as you mentioned, but also about their oral and nasal and sinus microbiome.

01:18:29.760 Where does that stand?

01:18:31.020 That is a contributor.

01:18:32.240 And guess what?

01:18:33.060 Sleep apnea.

01:18:34.040 Another big contributor.

01:18:35.560 So there are many, many different contributors.

01:18:39.040 And the idea that we're just going to find one thing is really not stacking up, given all of the data.

01:18:45.580 And so therefore, we end up with these things where, well, was this correct about the amyloid?

01:18:50.400 Was this incorrect about the amyloid?

01:18:52.380 It's a little bit like talking about a two-foot hole in the Titanic.

01:18:58.040 Well, it was that big, that huge one that really sank it.

01:19:01.440 Sure, the two-foot hole, I'm sure that that contributed a little bit.

01:19:04.320 But it's that big one that sank it.

01:19:06.960 So there are many different pieces we have to look at here.

01:19:10.540 And I think this is where medicine is headed.

01:19:13.480 What, is there a society on Earth where they really don't get Alzheimer's or dementia?

01:19:19.460 There are societies where there is less.

01:19:22.980 But there, other than people dying young, it is all over the world.

01:19:27.660 But yes, for example, it's been argued that people who, you know, who eat curcumin, for example, people in India, as you can imagine, part of the problem here is curcumin, yeah, turmeric, which happens to have a nice anti-inflammatory property.

01:19:43.600 And this has been eaten for, you know, thousands of years.

01:19:47.240 And yes, there seems to be a little bit less in that particular group.

01:19:51.880 And of course, there are others, some areas, for example, Okinawa, where people live long lives and have, in general, longer health spans.

01:20:01.320 Of course, Dan Buechner's Blue Zones, so-called.

01:20:05.720 But the answer is no, there's no place where people simply don't get it.

01:20:09.880 This is a common problem.

01:20:11.540 And in the United States of the currently living Americans, about 45 million of us will die from Alzheimer's.

01:20:20.600 So it actually dwarfs the pandemic.

01:20:22.980 And of course, the pandemic is now associated with brain fog.

01:20:26.000 So I think, you know, these are important areas going forward to optimize brain health.

01:20:33.060 Let's not wait for that single therapy, that drug that may never come, that is the cure for Alzheimer's disease.

01:20:40.880 All right, a couple other quick questions.

01:20:42.240 Is there a diet, you know, keto, paleo, intermittent fasting?

01:20:46.500 What would you say, you know, we should be doing if we want to prevent this?

01:20:50.580 And again, it's part of the overall piece that you need to look at what's driving the problem.

01:20:54.600 So for some people, it's going to be very important.

01:20:56.460 Some people, not quite as important.

01:20:58.160 But yes, the biochemistry that needs to be addressed by the diet is, number one, you need to get people into mild ketosis.

01:21:05.900 That's one to four, what they call millimolar beta-hydroxybutyrate.

01:21:09.940 So a little bit of ketosis is helpful.

01:21:12.020 And why?

01:21:12.740 Because your brain runs on only two different types of energy, glucose, ketones.

01:21:18.240 As we get older, we lose the ability to do both.

01:21:21.300 And people with Alzheimer's tend to have lost both.

01:21:23.640 They have the insulin resistance that means that they don't use glucose well.

01:21:27.900 And by the way, the PET scans, that's exactly what they show, that the brains don't use glucose well.

01:21:33.500 But they're also not keto-adapted.

01:21:36.200 They're not making and using ketones.

01:21:38.940 So that's the first piece.

01:21:40.260 It should be plant-rich.

01:21:42.000 It doesn't have to be just plants.

01:21:43.320 But plant-rich for all the phytonutrients should be high fiber and should be colorful and should be associated with a period of fasting that allows you to be metabolically flexible.

01:21:57.000 And that means able to burn glucose, able to burn ketones.

01:22:00.620 Most people, as I mentioned, who have Alzheimer's or pre-Alzheimer's are unable to burn either of those.

01:22:08.480 Last time we were on, you mentioned coffee.

01:22:10.820 My husband gave it up for, I don't know why, but he started to resume because of the brief conversation we had.

01:22:17.040 But coffee could be good.

01:22:18.720 Absolutely, and some beautiful work out of University of Florida has shown that, in fact, coffee, it reduces your likelihood of developing Alzheimer's.

01:22:29.840 So, yes, it's got some issues.

01:22:31.740 You know, it can be stressful for your adrenals.

01:22:33.820 It can interfere with your sleep, of course.

01:22:36.360 But it does, in terms of just epidemiology, it is associated with a lower likelihood of developing Alzheimer's disease.

01:22:44.100 Women get it more often than men, at least in America.

01:22:49.600 And I was sitting there getting my hair done before the show today, and I was thinking, I was breathing in all the toxins from the hairspray and the other products that she uses.

01:22:59.920 And I was like, this is why.

01:23:01.500 This is why.

01:23:02.460 And I was like, we should do a study to see whether news anchors or actresses or people who have to get their hair done or women who work in hair salons get it more often than women just who have naturally gorgeous hair and don't need all that nonsense.

01:23:14.460 I'm telling you, it's like the toxins.

01:23:15.820 That's what I'm going for, the toxins.

01:23:17.380 And also, why the women?

01:23:19.520 It's a great point.

01:23:20.600 And as Maria Shriver has told us for years, this is a woman-centric disease, almost two to one. 1.00

01:23:25.780 About 65% of the patients are women, and about 60% of the caregivers are women.

01:23:31.960 So this is a huge issue.

01:23:33.980 And part of the reason may be because of the rapid hormonal change during menopause, where you lose estradiol rapidly, because estradiol does have a beautiful anti-Alzheimer effect.

01:23:45.840 And as you indicated, exposure to toxins, we've been very surprised at how commonly toxins are one of the important contributors to cognitive decline that turns out to be associated with Alzheimer's disease.

01:23:59.240 So, yes, you may be right.

01:24:01.060 It may be time for you to write a paper on that.

01:24:03.600 I mean, you're just going to have to have flat hair.

01:24:05.540 What about drinking?

01:24:06.840 I mean, we always joke like, oh, I killed some more brain cells.

01:24:09.800 Are you actually killing brain cells?

01:24:11.380 I mean, are you killing the things that help memory and, you know, that you'll need to stave off dementia?

01:24:16.120 Yeah.

01:24:16.600 Yeah.

01:24:17.360 And so, as with so many other things, there's a positive and a negative.

01:24:21.020 Yes.

01:24:21.700 No question.

01:24:22.820 Ethanol is a neurotoxin.

01:24:25.720 So, unfortunately, when we drink, yes, we can damage some neurons as well as other things.

01:24:30.780 But it would also, in general, when people are drinking, it's relaxing them.

01:24:36.320 Lower stress is better.

01:24:38.400 People who are drinking tend to have a little better, a cleaner vasculature.

01:24:42.860 So, there's, you know, there's both sides here.

01:24:45.160 But overall, yes, you don't want to be drinking to the extent that it impairs your cognition.

01:24:50.660 How do you find out if you're somebody who has inflammation, right?

01:24:54.960 I think most of us, especially all my women friends, we all feel inflamed at the end of the day.

01:24:59.420 You know, you look good in the morning.

01:25:00.640 You're like, I'll go to the beach now.

01:25:02.000 If somebody told you you had to go to the beach at 11 p.m., you'd be like, hell no, right?

01:25:05.400 Because, like, so does that mean we have inflammation or is that just being a human?

01:25:09.760 Great point.

01:25:10.520 So, you know, we all know when you turn 50, what do you do?

01:25:13.940 You go get a colonoscopy.

01:25:16.060 So, if you're 45 or over, you should get a cognoscopy.

01:25:20.740 Blood tests, simple online cognitive test.

01:25:24.560 And then if you have symptoms, you want to include an MRI with volumetrics to look at the various regions of your brain.

01:25:30.520 But if you're asymptomatic and just for prevention, don't need to do that third part.

01:25:34.480 Everyone should do this.

01:25:35.820 When you do this, you look at blood tests.

01:25:37.880 Unfortunately, many of these not being done by doctors who are treating Alzheimer patients.

01:25:42.340 But they tell you if you have inflammation or if you have insulin resistance.

01:25:46.600 And as an example, there are multiple ways to look at inflammation.

01:25:50.180 HSCRP is the one you want.

01:25:51.440 It's the simplest, quickest.

01:25:53.320 This is high sensitivity C-reactive protein.

01:25:56.840 It's made in your liver.

01:25:58.280 And it is something that responds to inflammation.

01:26:02.260 I'm writing that down right now.

01:26:03.600 HSCRP blood test.

01:26:04.680 Okay.

01:26:04.800 I don't know whether I've ever had that done.

01:26:06.120 But I did take the cognitive test on your website.

01:26:08.820 Is it your website?

01:26:10.080 Yeah, I think it's yours.

01:26:11.360 This morning, Apollo.

01:26:12.760 That's you, right?

01:26:14.140 Yeah, I'm a consultant for Apollo.

01:26:15.580 That's correct.

01:26:16.480 Okay.

01:26:16.820 So I took your cognitive test this morning.

01:26:19.100 And it's actually kind of fun.

01:26:20.060 I recommend people go there and do it.

01:26:21.400 It took, you know, 10 minutes.

01:26:22.880 And you're basically just pressing shift or enter and like sort of saying yes or no to the questions.

01:26:28.360 But so I came out average, which I was like, okay, I'll take average.

01:26:32.460 I definitely did not think I was above average when it came to my memory, but it's always been weak.

01:26:37.120 So when your memory's always been kind of weak, like, you know, do you forget long ago memories?

01:26:43.560 Yes, but my whole life I have, you know, I mean, I didn't have that many long ago when I was 25.

01:26:49.460 But I've never been good at remembering the specifics of stories from long ago.

01:26:53.100 I just have always had a bad memory.

01:26:55.080 So what does that tell me?

01:26:56.600 And being average at 51, what does that tell me?

01:27:00.160 Yeah, well, of course, first of all, you wouldn't be able to do what you're doing without being very sharp.

01:27:05.880 But each of us has different, as we all know, we all have different challenges and we all have different strengths.

01:27:12.140 And what you're describing is common.

01:27:13.780 You're saying that memory has not been your strong suit since you were younger.

01:27:17.300 And so that's a very important point, because what we're looking for, which is, again, why everyone should have a baseline if they're 45 or over, is that we want to know change.

01:27:28.980 And so we've had an example for one example where a guy who was the math champion of his entire state began to have very significant dementia.

01:27:39.280 And his wife took him in to see a neuropsychologist who said, oh, great news, you're scoring in the 50th percentile, so you have no problems.

01:27:47.860 And his wife said, are you kidding?

01:27:48.960 This guy, it was a genius.

01:27:50.740 He has fallen so far from where he was.

01:27:53.400 So you want to know, have things changed?

01:27:56.880 And this is unfortunately what, when the first test you ever take, you won't know that.

01:28:00.980 You need to go, you know, you need to go several times over time to know whether things have changed.

01:28:07.740 But by the way, there are things you can do to strengthen your memory.

01:28:11.720 Part of this is about performance.

01:28:13.860 This is not just about decline.

01:28:16.020 It's also about having all of us perform better.

01:28:20.440 What can you do?

01:28:21.080 Because let's say I get the blood test.

01:28:22.780 I mean, does that blood test, that's not the one that tells you whether you have a gene that's going to give you Alzheimer's.

01:28:28.440 Like, that's knowable, too.

01:28:30.040 And that's the one I was talking about in the tease, where most people are like, I don't want it.

01:28:33.860 You know, it's interesting.

01:28:34.860 The establishment has told us, don't bother to check this because there's nothing you can do.

01:28:39.920 And nothing could be further from the truth.

01:28:41.780 There's a tremendous amount that can be done.

01:28:43.860 And so, yes, the gene you're referring to is APOE4.

01:28:46.640 It's one of dozens of genes associated with increased risk for Alzheimer's disease.

01:28:51.460 But it is not your fate.

01:28:53.100 Now, we have zero copies, one copy or two copies.

01:28:57.240 So you may have one from your mother or your father or both or neither.

01:29:00.700 And so when you get this test, three-quarters of us are APOE4 negative.

01:29:06.940 Our lifetime risk is about 9%.

01:29:09.140 Not zero, but it's not too high.

01:29:11.260 75 million Americans have a single copy.

01:29:14.340 30% chance during their lifetime that they will develop Alzheimer's disease.

01:29:18.380 So great to get on active prevention.

01:29:21.680 There's an entire group on the Internet, for example, ApoE4.info.

01:29:26.640 Check it out.

01:29:27.200 Over 3,000 people who all are APOE4 positive doing things to prevent their own cognitive decline.

01:29:35.140 And then 7 million Americans have two copies.

01:29:38.760 Their chance of developing Alzheimer's during their lifetime, well over 50%.

01:29:43.380 So in all likelihood, they will.

01:29:46.500 There's a very good chance that they will develop it.

01:29:48.620 Again, please get on active prevention so that we really can make Alzheimer's a much less common disease.

01:29:56.000 That's so crazy.

01:29:57.540 Like, truly, that is so uplifting because I'm one of those people who's like, I'm afraid.

01:30:04.500 I'm afraid to find out.

01:30:05.560 I did not have any testing.

01:30:07.580 I did have the colonoscopy at 50.

01:30:09.460 I had a bone scan, which actually did find some issues, which I've addressed.

01:30:12.980 And now I'm perfect in the bones.

01:30:15.640 But I never had this done.

01:30:17.480 And now I'm already worried that I waited too long.

01:30:19.400 I waited six years after 45.

01:30:20.960 It's not too late, though, right?

01:30:21.960 I can still get it done and get the blood test done.

01:30:24.260 You can do it at 75.

01:30:25.720 I mean, it's just that you want to do it.

01:30:27.620 As you hit 45, you want to be thinking about it.

01:30:30.480 When you get Alzheimer's, as you know, you go through these four phases.

01:30:34.060 Pre-symptomatic, where you can already pick it up on a PET scan, but you don't have symptoms.

01:30:37.940 There's SCI, subjective cognitive impairment, which lasts about 10 years, where you know

01:30:42.640 something's wrong, but you're still able to score in the normal range on testing.

01:30:47.180 MCI, mild cognitive impairment, which is pre-Alzheimer's, but that's the third of four

01:30:51.980 stages.

01:30:52.420 And then, of course, dementia, the fourth, Alzheimer's disease, where you're now losing

01:30:56.600 your activities of daily living.

01:30:58.120 If we could get everybody to get on prevention or earliest reversals, we could make this disease

01:31:04.800 much less common.

01:31:06.600 So I think you're a perfect age to do this, and I think it's a good idea.

01:31:10.700 We mentioned the ApoE4, but it will look at other things.

01:31:13.540 It'll look at your homocysteine, which is a measurement of several things, but including

01:31:18.040 inflammation, also your methylation, your ability to detoxify, things like that.

01:31:23.160 And it'll look at things like, do you have specific pathogens?

01:31:26.580 Do you have specific toxins you're exposed to?

01:31:29.040 Do you have underlying vascular disease?

01:31:31.380 These are all potential contributors to cognitive decline that can ultimately manifest as Alzheimer's

01:31:38.080 disease.

01:31:39.120 When you say ApoE, I just want the audience to know it's A-P-O-E-4, and the website is .info,

01:31:46.940 right?

01:31:47.320 .info?

01:31:48.040 Yes, .info.

01:31:49.200 That's correct.

01:31:50.300 And that is an apolipoprotein.

01:31:52.300 And so it's a protein that carries around fat.

01:31:55.320 So, you know, this thing is like your butcher.

01:31:57.060 It's the guy that carries around the fat.

01:31:59.380 And it had been unclear why it is that that thing actually is so associated with Alzheimer's.

01:32:05.160 Well, it turns out this impacts many of these factors that we talked about.

01:32:09.540 For one thing, it is a pro-inflammatory gene.

01:32:13.500 And it is something, by the way, the one that's associated with Alzheimer's was the primordial

01:32:18.040 one.

01:32:18.380 So the initial hominids, five to seven million years ago, walking along the African savanna 1.00

01:32:24.480 were all ApoE 4-4.

01:32:26.720 It helps them to survive because it's pro-inflammatory.

01:32:31.720 For example, you can eat raw meat more and better and with more impunity if you are ApoE 4-positive.

01:32:40.820 In third world countries, you survive better and do better if you're ApoE 4-positive.

01:32:47.040 So something we should all know, and we should all know this whole set of things so that we

01:32:51.640 know what our risk factor is.

01:32:54.100 So final takeaway for the audience members who are sitting there, because everybody thinks

01:32:57.680 they have Alzheimer's.

01:32:58.640 I mean, you know that, right?

01:32:59.640 You're a professor.

01:33:00.220 Everybody's like, I've got it.

01:33:01.140 I know I've got it.

01:33:02.500 For the people sitting there saying, I got it.

01:33:04.240 I know I got it.

01:33:05.020 So what are the two or three action items they need to do today?

01:33:10.400 Yeah.

01:33:11.060 So, you know, this is such an important point because you're right.

01:33:14.880 We are all at risk and about 15% of our population dies of Alzheimer's disease.

01:33:19.520 And we can do something about it for so many years.

01:33:23.000 So if we can just get people to come in earlier, better.

01:33:26.060 So the first thing, the most important thing to do is find out your risk factors.

01:33:29.980 Find out what your blood tests actually show.

01:33:34.040 But then beyond that, there are seven basics.

01:33:36.980 And we talked about some of these before.

01:33:38.960 And they are diet, exercise, sleep, stress, brain training, detoxification, and some targeted

01:33:46.720 supplements.

01:33:47.400 And people say, well, supplements aren't a cure for Alzheimer's.

01:33:49.720 Of course they aren't.

01:33:51.140 But the idea of optimizing your brain chemistry so that you reduce your risk is excellent.

01:33:56.900 And so we talked about the type of diet, you know, exercise.

01:34:00.280 There are some wonderful things coming up, things like katsu bands, which were used by

01:34:03.740 some of the Olympians, and what's called EWOT, exercise with oxygen therapy.

01:34:08.320 Beautiful study out of Israel recently showed how important hyperbaric oxygen was in some

01:34:14.200 people with cognitive decline.

01:34:15.480 Not for everyone, but for some people.

01:34:18.240 Sleep.

01:34:18.820 There's a whole huge, as you know, you know, beautiful works from Arianna Huffington on sleep

01:34:24.900 and also from Professor Matthew Walker from UC Berkeley.

01:34:28.900 It's a huge, huge part of all this.

01:34:32.180 Stress, another one.

01:34:33.640 Brain training.

01:34:34.540 Professor Mike Merzenich was the pioneer in brain training.

01:34:37.900 So all of these things are absolutely critical.

01:34:40.800 And then targeted supplementation and detox.

01:34:43.200 We are all exposed, just as you indicated earlier, to these various beauty products and

01:34:48.420 things, as well as food, as well as air pollution and things.

01:34:51.140 So, yes, there's a tremendous amount that we can all do.

01:34:55.720 Okay.

01:34:56.280 And the one-stop shopping, I know your book is The End of Alzheimer's, but like if they

01:35:00.140 want to go to one website to find this information, what is it?

01:35:03.800 You can go to drbredesen.com.

01:35:05.960 That's probably the easiest way to do it.

01:35:08.320 You can go.

01:35:08.800 That's B-R-E-D-E-S-E-N. 1.00

01:35:12.800 Doctor, I love talking to you.

01:35:14.960 Please come back often.

01:35:16.520 This has been so illuminating.

01:35:18.520 There's so much to be done.

01:35:19.640 Thank you, Megan.

01:35:20.180 All the best.

01:35:22.920 Thanks for listening to The Megyn Kelly Show. 0.94

01:35:24.820 No BS, no agenda, and no fear.

The Megyn Kelly Show - August 15, 2022

A Deep Dive Into Alzheimer's and Disturbing New Scientific Findings, with Dr. Dale Bredesen, Dr. Matthew Schrag, and Charles Piller ｜ Ep. 373

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