THINKWELL

AGEWELL

Rethinking Alzheimer’s: Dr. George Perry Challenges the Amyloid Hypothesis

00:00:00:00 – 00:00:23:04
Speaker 1
Until recently, many Alzheimer’s Associations advocacy groups had said. Working for the cure. You know, you don’t hear that among the heart Association. They don’t work for the cure. They worked for treating patients to give them a longer, better life. I think that Alzheimer disease, maybe in the long run there will be a cure. But I think that’s very far out of sight.

00:00:23:06 – 00:00:30:13
Speaker 1
And as long as we work for cure, I think we’re wasting our time.

00:00:30:15 – 00:00:53:17
Speaker 2
Welcome back to the Think Well Agewell podcast. I’m your host, doctor Heather Sanderson, and today I’m joined by my friend and co-host, Doctor Robert Love. Together we’re here exploring some of the most meaningful conversations at the intersection of brain health, aging, and hope. Our guest today is someone whose name carries enormous weight in our lives and in the field of Alzheimer’s research generally.

00:00:53:18 – 00:01:14:00
Speaker 2
Doctor George Perry is a professor of neuroscience, developmental and regenerative biology and holds the Seems Foundation Distinguished University Chair in Neurobiology and is the former Dean of Sciences at the University of Texas at San Antonio. Doctor Perry has studied Alzheimer’s disease since 1982, before I was born.

00:01:14:03 – 00:01:15:14
Speaker 3
That was the year I was born.

00:01:15:16 – 00:01:18:22
Speaker 1
Wow. And while you’re making me feel especially old.

00:01:19:00 – 00:01:50:00
Speaker 2
You are especially wise and experienced. And he was the first to discover that oxidative stress is a key feature of this and related neurodegenerative diseases. His studies identified oxidative damage, its source from metabolic and mitochondrial failure, and catalysts by iron and copper. I use this day to day in my clinical practice, and this work has led to a novel interpretation of the role of amyloid that instead of causing Alzheimer’s disease, that it’s a protective antioxidant response.

00:01:50:02 – 00:02:17:22
Speaker 2
And the reason all the amyloid based therapies has failed. You can see why we are excited to talk to a doctor, Perry, and why we even invited him here today. Doctor Perry is also the only known member of the Academies of Science of Portugal, Spain and Mexico. He’s also a prolific contributor to the Alzheimer’s research in general. In addition to being the editor in chief and a founding editor of the Journal of Alzheimer’s Disease, where Doctor Levin, I have both published our research.

00:02:18:00 – 00:02:22:23
Speaker 2
Doctor Perry, we are delighted to have you here. Thank you for joining us.

00:02:23:00 – 00:02:28:19
Speaker 1
I’m honored to be here and be able to speak to your listeners today.

00:02:28:21 – 00:02:53:08
Speaker 2
So you have throughout your career challenge to kind of the conventional thinking and the amyloid mafia, the amyloid hypothesis along the way. I’m curious. You know, this brings up some of the most complex and controversial topics in neurodegeneration. You know, can you give us sort of a CliffsNotes of your career and how you ended up in this position of disagreeing with some of your respected colleagues?

00:02:53:10 – 00:03:23:17
Speaker 1
Well, it isn’t so much I disagree. It’s that I listen to the data and interpreted, all of it collectively. But I think one of the reasons why I have a different view is my training prior to 1982, my PhD is in marine biology. My undergraduate degree is in zoology, but it was basically marine biology, which meant I studied animals and other organisms in their environment and understand how they adapted to it.

00:03:23:19 – 00:03:53:17
Speaker 1
And one of the key things about adaptation is that you generally successful organisms have changes that are important for their survival. There’s some consequence of not having adaptations for survival, and it’s called death or extinction, depending whether you deal with the species or the individual. And one issue for you once is that we’re definitely not going extinct, at least not in the short term.

00:03:53:18 – 00:04:34:06
Speaker 1
And we’re super successful, maybe too successful in terms of impact on the environment and Alzheimer’s disease changes. Whether it’s tau changes or amyloid changes or common changes. And all of the super sophisticated molecular genomics proteomics work. Still lives with an idea that’s over a century old. Alzheimer’s described a woman, in that case, a rather younger woman, middle aged, late middle aged in her 50s, who had a demented illness and an autopsy, had plaques and tangles.

00:04:34:08 – 00:05:04:12
Speaker 1
We haven’t gone over that. So if you have, your definition is that it’s really simple to say. All of the plaques and tangles cause the disease, and the genetics says the same thing, because the genetics of mutations and amyloid being associated with the disease, as well as the pathways of production of amyloid. Presnell in one, Presnell and two also play a role in amyloid production.

00:05:04:14 – 00:05:37:09
Speaker 1
So you can come to this conclusion causation. But all has been demonstrated by all this is no more than what Alzheimer himself demonstrated. Plaques and tangles are associated with the disease by definition. The genomics showed that the plaques and tangles where the plaques particularly are strongly associated and play some role. They’re not passive changes. They’re not just tombstones that that pathway plays an important role, but they don’t demonstrate what role it plays.

00:05:37:11 – 00:06:10:09
Speaker 1
In fact, the best demonstration of this was removal of amyloid by the antibody approach. And the patients didn’t get better. And you can come up with all sorts of hand-waving that it was too late, too early or too whatever it is. But no one had better. And and it’s not testable by other means. So we’ve still been fixated on one particular pathway, and I think it stems from that whole issue of how we approach disease.

00:06:10:09 – 00:06:46:22
Speaker 1
Chronic diseases are quite different than acute diseases. They are not necessarily single factorial and they really mesh with the biology. It is not the same thing as getting hit in the head, neither getting better the next day or dying or having major brain damage instead. Aging is associated with multi compensations. And all of us that are over 40 know that we change as we age and and yet we maintain normal function, some of us beyond a hundred years of age.

00:06:47:00 – 00:07:22:16
Speaker 1
Whether you have amyloid in your brain or not. Maybe that’s a it’s signaling that the brain is responding. So that’s been the basis of my studies. I didn’t come to that conclusion just because I was trained as a marine biologist. I came to it by looking at the effect of amyloid on cells and on animals in various formats, and found that it actually could be neurotrophic, that it could be cause gliadin responses, and also it has a strong antioxidant response in terms of how it interacts with metals.

00:07:22:22 – 00:07:24:18
Speaker 2
And anti-microbial as well. Right.

00:07:24:20 – 00:07:28:10
Speaker 1
Correct. But those are not my studies.

00:07:28:12 – 00:07:52:21
Speaker 2
So you’ve contributed again prolifically to the research by. It sounds like applying the principles of just good science, but wanting to understand what is true, not wanting to prove a hypothesis, but really from a genuinely curious perspective of what is going to work, what is going to support neuronal health and that field in general, as documented in doctor?

00:07:52:22 – 00:08:12:05
Speaker 2
Excuse me not doctor in the journalist Charles Pillar’s book doctored really describes you. You’re a leading character in this book, and a hero, if you will. It describes how the field has really gone awry, especially from a research perspective. Can you speak to any of that? And like where we went wrong?

00:08:12:07 – 00:08:48:12
Speaker 1
Well, first you you made a very good point. One of the key lessons I learned from the time I was a graduate student, when you’re trying to prove proof and quote Mark something in science, the best way to do it is to try to disprove it. You try to do everything you can to show your original ideas wrong, which I think is pretty schizophrenic, because there you are, you know, tying yourself to and a pertussis, and then you show it’s wrong.

00:08:48:14 – 00:09:15:06
Speaker 1
But you know what? You move on, you modify the hypothesis and modify it. Not an untestable ways, because, you know, most of the exciting things of life, like, you know, whether my wife really loves me and whether my kids are wonderful or not. How are those things testable? They’re not testable by science. Number one, I only have one wife, so that’s an end of one.

00:09:15:08 – 00:09:44:17
Speaker 1
So all of these things, you know, religion is the same way doesn’t mean that they’re not meaningful. But if you do things only to show what you’re your original hypothesis is true rather than to show it’s not true. You know, so the vaccine doesn’t work. The approach with the antibodies. Well, what do you do? You change your hypothesis, but you don’t change it to say, oh, well, we didn’t test it in the right way.

00:09:44:19 – 00:10:10:05
Speaker 1
I’ve seen it quoted saying, that the theory wasn’t wrong. We were the ones that were deficient in our testing of it. That’s not the way you do science. The way you do science is you develop ideas that fit the data, and you mentioned the idea of amyloid being anti-microbial. Well, if it’s anti-microbial, why is it causing the disease?

00:10:10:06 – 00:10:32:13
Speaker 1
I picture amyloid as being much like an inflammatory response. You have an insult and the insult to all of us, hopefully experience, which is aging, right. If we diet, you know, 30, we don’t experience very much aging, but if we live longer than 35 or 40, we’re going to experience some aging. And every year it’s going to be worse no matter what.

00:10:32:14 – 00:11:11:09
Speaker 1
Me too. Yeah. If we change our nutrition and we’ll talk about that later and things we can delay and certainly have a better aging process. But still, every day we’re older. And that insult, it’s like getting hit in the head a little bit every day. Not enough to kill you at any one time. And that’s what I view all the changes of aging be the responses that are there, and if those responses are inappropriate, which may happen with people with mutations because mutations that lead to disease, basically, or defects, and that puts them outside of evolution.

00:11:11:11 – 00:11:37:18
Speaker 1
You know, many of us have mutation and outside meaning those people will be selected against. And that is the case for amyloid precursor protein Presnell and one. Generally, the families are very small, which says that they’re selective disadvantage. I mean, the exception is his family in and Columbia, where it’s not actively selected against and not viewed as negative.

00:11:37:19 – 00:11:54:16
Speaker 1
So they have a large family. The same thing was true in Venezuela for a prion related family that was very large. But most families that have major mutations would have a problem in reproduction, and therefore they would be limited in extent.

00:11:54:18 – 00:11:59:06
Speaker 3
I wanted to ask you, some specific some controversial things. Yes. Book. The book doctored, but let’s.

00:11:59:06 – 00:12:00:05
Speaker 1
See if I can answer.

00:12:00:05 – 00:12:24:23
Speaker 3
Them. I recommend everyone read this book if it’s written like a murder mystery novel in science, and basically details how billions of taxpayer dollars have been wasted on the fraudulent amyloid hypothesis because some researchers prioritized their own fame and fortune, fudged their data, flat out, made up their data and this misdirected funds, and it got the wrong pharmaceuticals developed.

00:12:25:01 – 00:12:42:00
Speaker 3
Then the pharmaceutical companies start making up their data, and they start paying journals to publish their stuff, and then their stock goes up because they’re they’re in bed with the journal editors, not you. So you play you were the hero in this book. You are. Not only did they show how your journal does a very good job in peer review, write some journals.

00:12:42:00 – 00:12:58:06
Speaker 3
If if you pay, if basically if you pay the journal, they publish your stuff really quickly without revealing it. And pharmaceutical companies were basically doing that. Your journal doesn’t do that. Your journal is very good peer review. And then you were helping review some of the science to help, help the author, Charles Piller, figure out what was fraudulent.

00:12:58:06 – 00:13:16:15
Speaker 3
So I’d love to hear it. So I highly recommend this book to everybody. It’s awesome. I’d love to hear. What is your story with the author and, Doctor Schrag and and what was it like being part of this, of this great murder mystery to help reveal some of the fraudulent science that’s misdirected our field?

00:13:16:17 – 00:13:34:09
Speaker 1
Well, you know, it’s not straightforward. They mentioned particularly one particular article. And when Charles called me about this article and this was the one about the amyloid oligomers, the 12 year amyloid star.

00:13:34:11 – 00:13:37:08
Speaker 2
Out of the University of Michigan, it was a 2006.

00:13:37:10 – 00:13:39:21
Speaker 1
University of Minnesota.

00:13:40:02 – 00:13:42:06
Speaker 3
That’s all Cal State starts with them.

00:13:42:07 – 00:13:54:16
Speaker 1
Yeah, well, it’s close by. So in any case, he called me about this paper and also about the work in Austin.

00:13:54:18 – 00:13:56:12
Speaker 2
At that of a.

00:13:56:13 – 00:13:57:18
Speaker 3
Pharmaceutical work.

00:13:57:20 – 00:14:08:01
Speaker 1
Correct? Correct. Because harvest work was more limited in terms of scientific impact. It was the impact was more in the business end.

00:14:08:03 – 00:14:10:09
Speaker 2
But also in phase three clinical trials.

00:14:10:09 – 00:14:43:23
Speaker 1
Correct? Correct. Yes. I view that as part of the business. Yeah. Clinical trials, human health. Correct? Correct. And before you begin a phase three trial, the science should be solid because you’re putting patients at risk no matter even if it’s validated. And this was not validated data. It really was data that was suspect. Remember not suspect by me but suspect by others that are expert in image analysis.

00:14:44:00 – 00:14:46:02
Speaker 2
How did this happen?

00:14:46:04 – 00:15:10:06
Speaker 1
You know, I really don’t know. I really don’t know, but it’s not unique. Yeah. And in fact, I don’t think Charles Piller deals with there’s other cases. So I don’t know how I ended out becoming asked about data issues, but I was asked about another company. I’m trying to remember their name about suspect data. And again, I did not render an opinion on the data.

00:15:10:06 – 00:15:32:16
Speaker 1
I only rendered an opinion about what it meant if it was suspect. Mainly my comment always is that the data needs to be reproduced independently. That is for me the gold standard one is that you trust the people that produce the data, but you know, it’s spin set in politics. Trust and verify.

00:15:32:22 – 00:15:43:20
Speaker 3
Absolutely. What really upset me was that the the the the one of the lead authors from the University of Minnesota, she was very unrepentant. She basically got rich with grants because someone in her lab.

00:15:43:22 – 00:15:52:03
Speaker 1
Was rich with grants and many honors, including an Institute of Medicine membership and other things.

00:15:52:05 – 00:16:10:15
Speaker 3
Because her coauthor was cheating. And she said, I didn’t know about it. Okay, be nice if you knew what you were publishing. But let’s say she was innocent. But then they brought it back to her, and she was she was unrepentant. And she said, look, you’re not talking about the good things that I did. And then she tried to reproduce what she found, and she basically couldn’t.

00:16:10:17 – 00:16:33:08
Speaker 3
And they said, we can only reproduce this in our lab, but we think this is still valuable data. And I said, boy, you really don’t get it. She doesn’t understand that the work out of her lab that was published misdirected billions of dollars of research affected millions of potential patients and really affected the science. And she’s kind of bummed that she’s now just credit at the end of her career rather than saying, you know what, I made a huge mistake and this is bad science, and I’m sorry.

00:16:33:09 – 00:16:36:12
Speaker 3
She was completely unrepentant about the whole thing.

00:16:36:14 – 00:16:38:22
Speaker 1
That’s one way to describe it.

00:16:39:00 – 00:16:43:02
Speaker 3
Sorry. There’s not a question in there. There’s just outright in there that you helped uncover, you know.

00:16:43:02 – 00:17:13:05
Speaker 1
Well, you know, along that line now, this whole issue of the oligomers, and it’s not just the 12 mer, the whole issue of amyloid oligomers, ation, importance in the disease, whether it’s important, whether it’s part of the disease or not is very unclear. Very, very it was unclear from the very beginning. One is that you’d expect oligomers to be intermediates and formation of a large fiber.

00:17:13:07 – 00:17:20:03
Speaker 1
It’s not a surprise. You start with the monomer, it pieces grow. That’s in oligomers. You explain longer and longer.

00:17:20:04 – 00:17:25:19
Speaker 3
Two are not much of a group. So so amyloid plaque. You explain what the oligomers is. What why. That’s why.

00:17:25:19 – 00:17:45:13
Speaker 1
That’s why it is far more complex than that. So I can tell you that for a plaque, because we’ve done a lot of analysis, there are tons of things beyond amyloid, the Pi. But let’s just deal with the plaque as if it’s pure amyloid. So amyloid is a fragment of a large transmembrane protein, have around 700 amino acids.

00:17:45:15 – 00:18:10:00
Speaker 1
That protein is cut into pieces. One piece leaves from the inside of the cell. It goes through the membrane of the cell. The inside piece gets cut off, and the outside piece gets cut off. And the middle, which is part of the transmembrane, is the amyloid sequence, which is about 40 amino acids. That piece doesn’t like to be in water.

00:18:10:01 – 00:18:36:06
Speaker 1
It’s called hydrophobic fear of water. So it likes to stick together okay. And it sticks together with the other forms of itself. And when it does that, this is a super simplification that super little pieces kind of stick together and they form a filament. So you get little pieces all together. If you had little magnetic balls, they would stick together as magnets when they’re right.

00:18:36:06 – 00:19:04:08
Speaker 1
Orientation. And you have these filaments and those filaments bundled together to form a plaque. Okay. Before you get the plaque, before it gets to be large filament tube oligomers, people have made the issue that the oligomers of the toxic form of the amyloid. Okay, that might be true. They’re probably the more biologically active. I don’t know what it adds to the story.

00:19:04:13 – 00:19:21:02
Speaker 1
I never figured that out. So when he called me about this, I said this whole finding was trivial. And why would anybody pay attention to it? Then Mr. Piller pointed out that this work had been cited over 3000 times.

00:19:21:04 – 00:19:30:15
Speaker 3
For those of you not in science, that’s a huge number. The average number is 2 or 1 that a paper gets cited. Over 100 is pretty big. Over 1000 is a extremely important paper.

00:19:30:20 – 00:20:00:11
Speaker 1
Correct? Correct. Any paper over 1000 has major impact on the field. And what I realized in retrospect, in retrospect, after I thought about it for a day or two, because I’m not so swift at thinking of new ideas, is that, when I put the analogy, it was a stepping stone, the amyloid idea that we’re going to go through more as time goes on has had many folders, many, many.

00:20:00:13 – 00:20:26:18
Speaker 1
And every time it falters within a month or two, or even sooner, a new story emerges. Not a reformulation is saying, oh, we should abandon it. Look at it with fresh eyes. No, a new bandage. And I call them stepping stones if you’re trying to raise a child. When I tried to cross the creek that went near our house, I had to go out kind of stones in the deeper part.

00:20:26:20 – 00:20:50:06
Speaker 1
So if somebody put a stone there, it helped me get further along. And that is what the militaries always looked for, these stepping stones to keep it from falling into the river. And this oligomers story didn’t have to work forever, but you noticed that several people quoted. We didn’t believe the theory at all, and yet they cited it after they didn’t believe it.

00:20:50:08 – 00:20:53:23
Speaker 1
And that’s particularly disingenuous since the scientists caused.

00:20:53:23 – 00:21:08:14
Speaker 2
But then did I also understand that the oligomers theory. It’s helpful. It’s convenient if you’re a pharmaceutical company looking for a single agent to target, but yes, that part of the brain is well.

00:21:08:16 – 00:21:15:06
Speaker 1
Well, the pharmaceutical industry is looking for single targets to make people care.

00:21:15:08 – 00:21:15:17
Speaker 2
Right?

00:21:15:18 – 00:21:41:06
Speaker 1
What they promised with the amyloid cascade is one of my analogies. Promised to go to the Lords to go with the wheelchair. You get the amyloid treatment and you get out of the wheelchair. You know you’re treated. But to my knowledge, that is not work for any chronic condition. Whether it’s hard to see arthritis or the others the best we do is treatments that change the course of the disease.

00:21:41:08 – 00:22:12:10
Speaker 1
Alzheimer’s disease, instead of trying to look for change in the course, has actually focused on cures. And to my knowledge, there’s no cure for chronic age related disease. Of course, we hope there will be, but we’re very far from it. The best we do in Alzheimer’s disease is aricept cholinergic, which improves neurotransmitters in the patients. To get a bit better, at least some of them, and the side effects are very small.

00:22:12:12 – 00:22:47:01
Speaker 1
The amyloid approach has fell short of that. And furthermore, the greatest benefit has come from Alzheimer disease is lifestyle modification. Exercise such as the winner of the Alzheimer Prize mark. The Alzheimer Prize from Chad. We’re given the prize the best publication and the prior year. But exercise sugar modification, you know, lowering glucose levels, lowering stress levels, all of those things change the course of disease.

00:22:47:01 – 00:23:13:07
Speaker 1
They don’t eradicated. And if you look at instead, until recently, many Alzheimer’s associations, advocacy groups has said working for the cure. You know, you don’t hear that among the Heart Association. They don’t work for the cure. They work for treating patients to give them a longer, better life. And, I think the Alzheimer disease, maybe in the long run there will be a cure.

00:23:13:09 – 00:23:41:00
Speaker 1
But I think that’s very far out of sight. And as long as we work for cure, I think we’re wasting our time. We barely understand the disease from a biological standpoint. We barely know how it relates to neuronal death, relates to synapse loss. All the things that fundamentally have been said for Alzheimer disease has been primary, and the disease actually had very poor evidence for them.

00:23:41:02 – 00:24:04:11
Speaker 3
It’s amazing to me that you say there’s so much about this disease we don’t understand. You founded or co-founded one of the top journals in the field on this disease. You know more about this than almost anybody. I’d love. I’d love to hear. Why did you do that, Doctor Perry? Why did you go about creating and serving as editor in chief of a new journal that’s also been very bold and questioning the status quo.

00:24:04:11 – 00:24:13:12
Speaker 3
And status quo is been extremely, you know, unsuccessful amyloid mafia style papers, that haven’t been been very helpful. So why did you do this?

00:24:13:14 – 00:24:44:04
Speaker 1
Number one, we published papers on the amyloid a century people. We do not exclude papers from any idea. Okay, that’s really critical. So Journal of Alzheimer’s Disease was founded to form a community of investigators. For one thing, when you publish in Journal of Alzheimer Disease, you become a member of the editorial board for a year. And we hope that people will actually recruit articles so that it goes beyond my pedestrian interest.

00:24:44:06 – 00:25:08:11
Speaker 1
And the other part is we really want to embrace new countries, you know, like third world countries. They have initiative for getting more Africans to publish. We also had prior ones for South America, and we tried to have new ideas. That’s why we if you want to have a high impact factor, you publish things that are in the dominant idea.

00:25:08:11 – 00:25:38:17
Speaker 1
I’m not against having a high impact factor, but not at the expense of excluding third world countries and not at the expense of having new ideas. And, the way we have that we publish more articles than everyone else this year between Journal of Alzheimer’s Disease and, Alzheimer’s Disease Reports, which is our sister open access journal, we will publish very close to a thousand articles.

00:25:38:18 – 00:25:45:12
Speaker 1
And if you look at the other journals, it might be close to this number of all of them combined, but I’m not sure.

00:25:45:16 – 00:25:46:05
Speaker 3
And it’s.

00:25:46:05 – 00:25:47:15
Speaker 1
Probably not far from it.

00:25:47:17 – 00:26:03:05
Speaker 3
You do publish that, but I want people know that your, vetting process is is very strict. It took me years to write my paper. When I submitted it, I got some back, some very serious feedback that took me another couple months to incorporate. All right. It took me at least a month to incorporate and rewrite the paper to get accepted.

00:26:03:05 – 00:26:07:19
Speaker 3
So the peer review process happened at the Journal of Alzheimer’s Disease is is really top notch.

00:26:07:19 – 00:26:15:18
Speaker 1
We we try to we try, we try. But I cannot guarantee it’s always perfect and and balance regards it.

00:26:15:19 – 00:26:38:01
Speaker 2
Nothing is perfect right. That that’s not the standard the standard isn’t perfection. It’s a reproducibility. And I think that’s another thing that comes up in the scientific community is it’s hard to get published if you’re reproducing something right. If it’s already been published, what people are looking for is often the first right. The first time it’s published, that it’s unique, that it’s different.

00:26:38:03 – 00:27:02:01
Speaker 2
And if we really want to be good scientists, as you said, reproducibility is highly valued. And that’s really how I ended up in your in in the Journal of Alzheimer’s Disease with our paper is I was looking to reproduce what doctor Dale Bredesen had published. I had independently conducted a very similar trial in my office, and we were showing very similar results without his involvement.

00:27:02:01 – 00:27:13:05
Speaker 2
So it was done independently, and it would have been hard to get published in another journal because it wasn’t unique. But that’s not the value in it.

00:27:13:07 – 00:27:26:15
Speaker 1
Not only that, Doctor Pedersen just had a lot of issues, that people have been very critical of him. Yeah. And, you know, recently there was an article on New York Times very critical of him.

00:27:26:20 – 00:27:32:00
Speaker 3
Can we talk about this article? I love this article is it’s so bad, but I’d love your take on a New York Times article.

00:27:32:00 – 00:28:10:05
Speaker 1
Well, you don’t I’m not agreeing that everything Doctor Bredesen says is correct. Reproducibility is also the issue. But you can’t dismiss things without analyzing them. And here he is making claims that are revolutionary. People can be reversed. Whether that means that Alzheimer’s disease can be reversed. I think it still requires validation. But because one of the issues, I think with Alzheimer’s disease, especially in the initial phase, many cases are misdiagnosed.

00:28:10:07 – 00:28:41:06
Speaker 1
People that are older have a lot of reasons to have cognitive issues. Think about it. They may have lost a spouse. They may have financial problems. They may have physical issues because most older people have comorbidities. And if you can address many of those, you may be able to reverse the course of the disease instead of just coming into your general practice person and leaving with a prescription for aricept because you didn’t draw the clock right.

00:28:41:08 – 00:29:08:16
Speaker 1
I think really it’s important to understand why people are demented, and many of those conditions can be dealt with. And the main criticism I’ve had when reporters have asked me about his work and I’ve been misquoted along that line, they say it’s expensive. Okay, well, okay, what are the alternatives? If a person becomes tormented, they’re going to be in a nursing home.

00:29:08:20 – 00:29:37:05
Speaker 1
That’s going to be incredibly expensive, either for the person involved or society. If they get involved in these antibody trials, they’re incredibly expensive and put people at risk. Doctor Addison’s work does not put people at risk. They can discontinue it. And the cost, from what I know of it is not horrendous. So I just look at it in the broad spectrum that needs to be analyzed.

00:29:37:06 – 00:30:07:18
Speaker 1
And further, if it is successful, it can be upscaled and probably cost can be reduced when you start something and it’s small scale requires specialized training. That’s one thing, but this can be reduced. Number two, this idea that doctor Per Edison proposed has been around with a foundation. I’m associated with the Alzheimer’s Research and Prevention Foundation, which has a more narrow, treatment with four things that they suggest.

00:30:07:19 – 00:30:09:09
Speaker 2
Was four things.

00:30:09:11 – 00:30:45:12
Speaker 1
Four things exercise, nutrition, stress reduction, meaning in life. So are those, you know, with the 36 things that don’t represent proposals well, it’s more encompassing and not certain. Everybody can accomplish all 36. But the four things also can make a difference for people. And it puts Alzheimer’s disease in the sphere of other age related chronic conditions. And that, unfortunately, is not the way it’s been dealt with.

00:30:45:14 – 00:31:05:08
Speaker 1
Because Alzheimer’s disease is a part of our normal biology. You know, that doesn’t mean becoming demented. Is it part of our normal biology? But what’s happening in the brain is part, you know, all of us that are over 40 have some degree of amyloid already in our brain.

00:31:05:08 – 00:31:15:02
Speaker 2
Amyloid that we associate with Alzheimer’s disease as part of our normal aging. Normal. Right. I’ll correct these itself, hopefully is not part of our normal.

00:31:15:02 – 00:31:37:22
Speaker 1
But, you know, I think that that is part of the failure just is hard. Disease is part of the failure and arthritis is part of the failure. How the body deals with changes of the aging process. You can age and maintain normal function, which is what evolution is probably pushing for. But you can also fail along the way.

00:31:37:22 – 00:31:51:18
Speaker 1
And that’s what I view with the people with mutations that they fail much earlier, they fail in their 30s and 40s, and people without those mutations fail in their 70s, 80s and beyond.

00:31:51:20 – 00:32:10:05
Speaker 3
Now, what was your specific thought on the times article? So both Doctor Sanderson and I were interviewed for that article at length. And I thought the researchers you I thought you ask good questions. I agree the criticism is this month. It’s expensive. Try Alzheimer’s. That’s really expensive. However you’re going to do it.

00:32:10:07 – 00:32:15:07
Speaker 1
That is exactly where they say Alzheimer’s disease is expensive to everybody.

00:32:15:07 – 00:32:38:01
Speaker 3
Fish oils? Not so. I’d love to hear you. And then they really misquoted the science. They said it doesn’t work for everybody. That’s true. But it really works for seven out of ten people, according to Doctor Sanderson’s research. So I’d love to hear your thoughts on this, on analyzing the science, the article, because my concern is that that article is going to deter a bunch of neurologists from recommending diet exercise to their patients, saying, hey, this is expensive and it doesn’t work.

00:32:38:01 – 00:32:40:09
Speaker 3
Just just take the drugs right now and.

00:32:40:09 – 00:32:41:06
Speaker 2
It’s the French fries.

00:32:41:06 – 00:32:49:01
Speaker 3
Yeah, and eat it. And the article ends with your French fries, which is fascinating to me that that’s how they concluded the article.

00:32:49:03 – 00:32:51:14
Speaker 2
Were you interviewed by Lindsay Gelman? By the journalist?

00:32:51:14 – 00:33:16:17
Speaker 1
No, no, I learned about I been interviewed prior. I don’t remember when years ago. And that’s when I said I was slightly misquoted. Like I said, it was expensive or something like that, which isn’t what I said. I said Alzheimer disease is expensive in this is. Anyway, I don’t think that’s a big issue, even if this only benefited 10% of patients.

00:33:16:23 – 00:33:22:10
Speaker 1
Even if it only benefited 10% a patient, that would be revolutionary.

00:33:22:12 – 00:33:23:18
Speaker 2
And we see it even.

00:33:23:18 – 00:33:26:08
Speaker 1
If it benefited 1% of patients.

00:33:26:08 – 00:33:28:19
Speaker 3
So what, you’re seven out of ten, right?

00:33:28:21 – 00:34:01:21
Speaker 2
Well, 74% of the participants of that, it was a small study was a feasibility trial, 23 participants over six months who had measurable cognitive impairment on, on of course, we screened them with markers. But then we also looked at the Cambridge Brain Sciences battery of neurocognitive testing and 74% of those participants of 17 out of the 23 improve their cognition measurably and statistically significant improvement across the means of all participants in six months in overall composite cognition, memory, and in sleep and quality of life.

00:34:01:23 – 00:34:11:00
Speaker 2
So these have profound implications for people. I think that’s why it was so heartbreaking for me to read the article. After being interviewed at length.

00:34:11:02 – 00:34:41:15
Speaker 1
So I asked one of my colleagues about this, who has worked in the pharmaceutical industry there previously, and she told me, she said, do you realize that that was a hit piece for that? That the pharmaceutical industry does not want to have competition here? They’re launching these monoclonal antibodies. It is totally unclear whether patients really benefit from those trials.

00:34:41:17 – 00:34:44:15
Speaker 2
And it’s very clear that there’s extremely high risk.

00:34:44:17 – 00:34:48:08
Speaker 1
Correct. All the patients have brain shrinkage.

00:34:48:10 – 00:34:49:03
Speaker 3
Oh my gosh.

00:34:49:03 – 00:34:56:16
Speaker 1
And that has been true for every one of the trials. There’s 20 some trials that have been done. And when people have done imaging, the brain shrink.

00:34:56:18 – 00:35:00:00
Speaker 2
And do they call this pseudo atrophy, do I understand.

00:35:00:02 – 00:35:01:20
Speaker 1
I don’t know what they call it.

00:35:02:01 – 00:35:05:02
Speaker 3
Now is this targeted to amyloid as well.

00:35:05:04 – 00:35:18:18
Speaker 1
All these studies have talked about or antibody studies. Either they are passive immunization using monoclonal antibodies or prior studies which used antigen okay. No. And then having done.

00:35:18:20 – 00:35:20:16
Speaker 3
Plaque blockers.

00:35:20:18 – 00:35:23:21
Speaker 1
Yes, they theoretically removed the plaque.

00:35:23:23 – 00:35:24:07
Speaker 3
Okay.

00:35:24:07 – 00:35:26:23
Speaker 1
So there’s controversy on that. But let’s not go down.

00:35:26:23 – 00:35:29:19
Speaker 3
These are having amyloid plaque through monarch correct?

00:35:29:21 – 00:35:54:18
Speaker 1
Correct. And it’s been demonstrated there’s controversy on that point. But the autopsy of one of the people who died was a close colleague of mine, Rudy Castellani. You know, this woman that was reported New England Journal of Medicine was sailing with the family the week before she died and was had dinner the night she was admitted to the hospital.

00:35:54:18 – 00:36:20:04
Speaker 1
She went out for dinner. She was not bedridden, you know, she had mild cognitive impairment. She was a lawyer 65 years of age. And why was she so motivated to be involved in trials? Because she was in ApoE e4 for Homozygote. So she was at high risk, not a 100% risk, but theoretically ten times normal risk. Yeah, that is.

00:36:20:06 – 00:36:22:20
Speaker 2
Not a good candidate for getting the Kennedy.

00:36:22:22 – 00:36:55:18
Speaker 1
Correct. Now, we know that because you’re more likely to have Congo Pelikan trial. Patty and I wrote it together with Craig Atwood, Mark Smith many years ago. I wrote a short letter for science magazine, So Prominent Place, saying that the most likely outcome of treating amyloid would be cerebral hemorrhage. Why? Because the muscle layer we demonstrated in prior studies is, lost during Alzheimer’s disease because it gets replaced with the amyloid deposits in the vessels.

00:36:55:20 – 00:36:58:03
Speaker 2
You’re reducing the integrity of the blood vessel.

00:36:58:06 – 00:36:59:06
Speaker 1
Correct. And now you.

00:36:59:10 – 00:37:00:16
Speaker 2
Have high bridge.

00:37:00:18 – 00:37:17:23
Speaker 1
Correct. That the vessels are already compromised by replacement of the muscle layer with amyloid. And in fact, in some people with Alzheimer disease that have sufficient cargo Pelikan job that they they will have stroke spontaneously. So even without removing amyloid.

00:37:17:23 – 00:37:19:04
Speaker 2
Oh that’s holding.

00:37:19:04 – 00:37:38:13
Speaker 1
It’s even going to accentuate the problem. So we wrote this small note in science and followed it with the more a larger article on it, another journal going through why this would be a likely outcome among many studies that we had analyzed, that amyloid removal would be detrimental.

00:37:38:17 – 00:37:43:06
Speaker 3
You called these side effects well in advance of what was likely to happen.

00:37:43:06 – 00:37:45:18
Speaker 1
I think that was in 2003.

00:37:45:20 – 00:37:46:19
Speaker 3
Yeah. Thank you. Thanks.

00:37:46:19 – 00:38:15:15
Speaker 1
So we became a question in the amyloid idea beginning in the late 1990s, and wrote our first article in the year 2000, and it was in the journal Lancet, and it was called Amyloid Junkies being. Why do you think the amyloid removal will be a benefit? And the real test of the amyloid hypothesis will be when we do these trials to remove it.

00:38:15:17 – 00:38:49:03
Speaker 1
And then with the failure of those trials, at that point, we didn’t say that the idea was wrong. I said, why? Why are you so sure? And then we wrote saying, You’re Copernicus revisited the idea. You know, Copernicus was the one who suggested that the planets went around the sun rather than the reverse. And I pointed out which actually my coauthors who played the major piece in writing this article, I said, do you realize Copernicus work was published posthumously?

00:38:49:05 – 00:39:13:18
Speaker 1
That if you questioned things like this, he was afraid of being burned at the stake? Right, because people would question, and Galileo getting involved is more complicated than just him questioning it. He was kind of making fun of the Pope. So anyway, all these stories are complex, but he at least wasn’t burned at the stake. And his recanting.

00:39:13:19 – 00:39:38:19
Speaker 1
So any case, later on, when the antibody approaches didn’t work and the initial reports said that the patients actually got worse, the initial report said that then there was no more comments about patients getting worst. They just kept doing more and more trials with early years had patients and with different targeting oligomers. You remember. That’s why the outlook on life story was important.

00:39:38:21 – 00:40:05:21
Speaker 1
The reason us the studies removed amyloid, but they didn’t remove the toxic one. I thought it actually reminded me of the whole approach of needles, angels on the head of a pan, or any of those type of things. You’re looking for something that doesn’t exist and you’re making up new stories. You didn’t get the right one. And amyloid is clearly the evil.

00:40:05:23 – 00:40:28:10
Speaker 1
So you need to remove the evil and medicine as opposed to biology always seems to point out something is evil. To hear a talk that’s about medicine, they talk. This is the bad thing. Biology doesn’t have bad things. It just has things. And they’re all related to surviving. You know what a lion is wonderful to see at the zoo.

00:40:28:12 – 00:40:49:04
Speaker 1
But if I was in Africa and I wasn’t in a, you know, in a truck and a lion came to me, it wouldn’t be a very good thing, right? Because it’s a value judgment. So it depends. For me, amyloid depends on context. I think it’s doing its job, which we think plays an important role in cleaning up metals.

00:40:49:04 – 00:41:18:23
Speaker 1
So they don’t cause oxidative damage. But does that mean it could be out of control? Of course. Of course it can be. But that isn’t the rationale people show they always pointed to being evil. And so therefore I wrote a small thing, and I likened the idea of amyloid removal to exorcism and leeches. And, you know, the idea of bloodletting is not so old in in science.

00:41:19:01 – 00:41:50:06
Speaker 1
George Washington died of bloodletting. He had a minor illness, and the physician came in with true blood because the idea of humors, you know, this is back from Roman times. And 200 plus years ago, there was a year, 1800. So 220 years ago, probably the best medicine, I would imagine George Washington had the best possible at that point.

00:41:50:08 – 00:42:08:17
Speaker 1
Somebody came and removed his blood. And that definitely if you’re a little bit sick and you have more blood taken out, it doesn’t have a good outcome and it didn’t have a good outcome for him. So I think that people are always trying to remove something evil. And sometimes that works.

00:42:08:18 – 00:42:29:17
Speaker 3
So, doctor, I want to provide a little bit of context to catch everybody up who’s not who has who hasn’t read the book, is not really familiar with the data. So in around 2000, you published an article saying removing the amyloid plaque based upon the data is likely to increase problems in the brain, specifically strokes and problems. Problems there because can weaken blood vessels.

00:42:29:19 – 00:42:50:06
Speaker 3
And you wrote an article in the Lancet which one of the top journals in science about it calling people amyloid junky, saying, listen, you think amyloid is you think this is the biggest problem with Alzheimer’s? Where’s your data? Let’s see. And then the initial reports were you’re right, the Alzheimer, the drugs that block amyloid plaque, were causing more problems than they were solving.

00:42:50:12 – 00:43:13:12
Speaker 3
So that was a big first chunk of science on this. And then they kept changing the story. They said, well, maybe it’s not just in blood plaque, it’s a specific type of oligomers. And hey, we hey, we found it in the University of Minnesota lab and no one can replicate it. But look, look how clear it is on our fraudulent science, which is what the book doctor’s about, about that fake study and then other people saying, oh, and then up here citing the study and gets 3000 citations and it affects the literature.

00:43:13:12 – 00:43:30:16
Speaker 3
They said, oh, it’s not just invalid plaques. It’s it’s a specific oligomers. And then you got pharmaceutical companies saying, hey, we’re going to target this oligomers. And then they got their drugs in phase three trials. So that’s basically you correctly share what was going to happen 25 years ago with your two papers. You saw this coming in advance.

00:43:30:16 – 00:43:33:14
Speaker 3
So thank you for warning the side to community and and the people about it.

00:43:33:14 – 00:43:37:12
Speaker 1
When they didn’t stop people from continuing to fund this approach.

00:43:37:16 – 00:43:57:03
Speaker 2
Right. You know, if you could wave a magic wand at this stage in your career, what would you hope like the next few years of research look like? There’s a lot of changes happening. You know, I think it’s yet to be determined whether they’re good or bad or indifferent. There’s a huge shift in how money’s being spent at the NIH.

00:43:57:05 – 00:44:13:05
Speaker 2
And I’m wondering if you if you had control over that, like, what would it look like? What would be emphasized, what would be studied, how how would we go forward if our goal were to reduce the suffering associated with Alzheimer’s and dementia?

00:44:13:07 – 00:44:33:06
Speaker 1
For one, I wouldn’t discontinue studies on amyloid, the basic biology, because I think amyloid and tau play a critical role in the disease. But I don’t think that the data does not put them as positive. It puts them as critical in the pathway, because usually you have people that say they either cause and they’re everything, or they’re nothing.

00:44:33:07 – 00:44:38:18
Speaker 1
There’s a lot of differences. Yeah. And subtleties and things clearly correlated.

00:44:38:21 – 00:44:41:03
Speaker 2
They’re clearly part of correlated.

00:44:41:03 – 00:44:55:18
Speaker 1
And probably play a critical role in the pathway. Yeah okay. And they may be able to provide insights may okay. But there’s also tremendous like the work you’ve done to Burleson and others.

00:44:55:19 – 00:44:59:20
Speaker 2
At Dean Ornish. Yeah. Yes. There is a long list of people, a.

00:44:59:20 – 00:45:22:17
Speaker 1
Long list of people that put Alzheimer’s disease, much like other age related chronic conditions and which many factors play an important role. And what we’re looking at is one pathway of aging, which the system fails. Fails. By fails, I mean fails to lead a functional brain. The brain stops functioning except, you know, to maintain heartbeat, things like that.

00:45:22:19 – 00:45:52:02
Speaker 1
But it doesn’t maintain normal cognition. So I think we need to understand that much better. That means understand the idea of the infectious agent idea. How does that play a role, the role of diet, the role of diabetes, and a much broader biological sense and along that line, doing more clinical trials for amyloid, I don’t think is particularly valuable.

00:45:52:04 – 00:46:19:09
Speaker 1
Okay. I’ve been asked that. And people that are more in the government area, and I wouldn’t say that there, but I don’t think that they provide a lot of information of amyloid removal by itself is going to make a difference. That doesn’t mean it couldn’t work, but so far, wouldn’t the Tau story. Well, the logic used for tau is the same logic is used for amyloid.

00:46:19:11 – 00:46:46:09
Speaker 1
So I think it’s highly likely but not demonstrated that you end up with the same outcome. Tau also is associated with an antioxidant response. It’s different than the one of amyloid. It’s associated with an enzyme, heme oxygen Ace, which is an antioxidant enzyme. Wherever you find tau and Alzheimer disease, you find this enzyme Co localized. Why is Haynes important?

00:46:46:11 – 00:47:11:08
Speaker 1
Mitochondria contain a lot of heme containing enzymes, and mitochondria are getting turned over in cells. And that turnover needs to be you have to break apart the components. And heme is one of those components. The other one that components is metals. Heme is just like hemoglobin contains the iron which is responsible for the red color blood and cells.

00:47:11:08 – 00:47:40:23
Speaker 1
There’s little cytochrome s which are very similar to hemoglobin. Well in the broader sense. And they get turned over because cells are constantly changing out the proteins that are there, renewing them. And when you renew them, you release these battles. We think amyloid plays a critical role in those inner changes. In other words, binding the metals so that they don’t cause oxidative damage.

00:47:41:00 – 00:47:45:09
Speaker 2
Fascinating. So more research potentially down that vein.

00:47:45:11 – 00:48:00:03
Speaker 3
I have a question about town. I recently got to have a meeting with a CEO of research of a major pharmaceutical company. And I said, what do you do with Alzheimer’s? And he said, oh, we got this really great new treatments, by the way. He he’s in pharma. He love the New York Times article. He thought it was great science.

00:48:00:03 – 00:48:24:01
Speaker 3
And I had a few words for him about that because it was anti-science. So I said, what is what does it do? You said, well, we see tau tangles as being contagious. And so, if they’re cells next to each other, that’s if one cell has tangles in it. So for those of you at home, tau tangles have an inside of the cell inside the axon, whereas plaque happens outside the cell.

00:48:24:01 – 00:48:44:15
Speaker 3
So this is problems inside the cell. So if one cell has tail tangles the next cell is likely to get that. And part of that is phosphorylation. So they have a drug they’re developing drugs that prevent the transfer of phosphorylation from one cell to another. So it’s blocking the pathway of phosphorylation. And and they believe this will help, reduce tau.

00:48:44:16 – 00:49:15:01
Speaker 3
And this will help with Alzheimer’s. And my thought was, well, what’s causing the tau? You’re stopping the spread of it, but what’s causing it? And that this is an unwelcomed question to someone in pharma because they wants, as you said, a single target in a single pill that cures everything. So I’d love to hear your prediction, because this will probably be in the next 20 years, assuming their research shows any sort of promise this will in 20 years, we’ll be have this conversation about about Tau drugs.

00:49:15:06 – 00:49:24:13
Speaker 3
What are your thoughts on the likely outcome of reducing the phosphorylation from one cell to another? Involved in making of, these tau tangles?

00:49:24:15 – 00:49:58:19
Speaker 1
Well, number one, I don’t think we’re going to have to wait 20 years. There’s already studies on tau locking, and the initial ones have not shown benefit. But might it be different for the phosphorylation? Number one, you can never be certain any of my conjectures with regard to drugs in my work. Who knows. They might work, but if I’m making my best guess, my hypothesis is that this is still part of a normal response and therefore in fact, tons of data is shown.

00:49:58:19 – 00:50:04:22
Speaker 1
Tau phosphorylation occurs during early life when you’re a child.

00:50:05:00 – 00:50:11:13
Speaker 2
Yeah, you see this when we measure Peterhouse, they’re high in children and they’re also high when there’s plastic activity going on.

00:50:11:15 – 00:50:12:13
Speaker 1
Yes.

00:50:12:15 – 00:50:13:17
Speaker 2
So so how.

00:50:13:17 – 00:50:21:12
Speaker 1
Does that sound like that’s bad. So this summer marks 50 years that I’ve studied oxidative stress.

00:50:21:14 – 00:50:23:05
Speaker 3
Thank you for television to science.

00:50:23:05 – 00:50:52:13
Speaker 1
That’s. Oh thank you. So I began studying it in here. Trunk fertilization. So fertilization is something pretty essential to life okay. If you weren’t fertilized the egg of your mother and the sperm they didn’t join, you wouldn’t be here today. So your genes wouldn’t go forward. What happens right after fertilization is there’s an oxidative burst and some of that is lipid oxidation.

00:50:52:13 – 00:51:23:19
Speaker 1
Another part of it is naphtha quinone oxidation. And that’s what I discovered while I was a student. And so, you know, at that point in time, most people thought of oxidative stress as being something that was bad. And that’s what I considered to be the classic idea of oxidative stress. Classic idea I called a rusty nail idea when you’re born and when you’re vital, you’re shiny and bright and you’re able to fight off rusting.

00:51:23:21 – 00:51:44:06
Speaker 1
As you get older, you start to get little bits of rust on you. In fact, I remember asking a very prominent person about my work early on about assays because I didn’t know when I was a student how to assay oxidative stress very well. And I remember calling Al Tadpole, who is an expert on oxidative stress during that time.

00:51:44:06 – 00:51:51:10
Speaker 1
And but he studied mostly rancid, you know, basically meat or butter getting rotten.

00:51:51:12 – 00:51:52:13
Speaker 2
Oh yeah.

00:51:52:14 – 00:52:25:15
Speaker 1
Oils. They react with oxygen. Okay. That’s fine. What are you looking at when you look at rancid T, you’re looking at dead piece of meat or a piece of butter. It’s not living. The thing about that became more clear. And and I wrote several articles that people said were ahead a little bit ahead of other people because I was trying to understand why, unless I read disease, we found all this oxidative damage, and it was in cells that were still going to exist or another 20 or 30 years had the people lived.

00:52:25:17 – 00:52:53:02
Speaker 1
So we came up with this idea that basically oxidative stress is basically a homeostatic issue for chronic conditions. In other words, if you get hit in the head or you have an acute problems, yeah, oxidative stress occurs and you’re like the rusty nail and the outcome is you may die. But if you’re aging, you know you’re going to have more of this change every year because the underlying conditions are going to get worse.

00:52:53:02 – 00:53:19:20
Speaker 1
Maybe you exercise and you reset your clock a little better, you change state, but you’re still getting older. But in any case. So we came up with this idea that oxidative stress and damage was not necessarily deleterious. Is that buried in all of our papers? Not so clearly, because it’s easier to write about oxidative damage and it’s detrimental, but we really don’t know what it is.

00:53:20:00 – 00:53:27:00
Speaker 1
And I think that’s the same thing for tau. If it’s spreading into how do we know what it means?

00:53:27:02 – 00:53:29:05
Speaker 2
Well, we take it away and see what happens. Right.

00:53:29:05 – 00:53:59:13
Speaker 1
And then you mentioned earlier about synapse changes. So you know everyone talks about this synapse loss. There’s very poor demonstration of synapse loss and Alzheimer disease extremely poor. We completed the study. It doesn’t directly address synapse for us because we didn’t do it the morphology tree in that way. But the original studies were done by Steven Chef, who is currently at the University of Kentucky as an emeritus faculty.

00:53:59:15 – 00:54:28:21
Speaker 1
And he analyzed synapse density and Alzheimer disease and ALP electron microscopy. He did not find much of a change. The change that was noted was changes and Synaptic Vesicles by Robert Terry and Eliza Bosley, whose name is mentioned prominently in this book. He, modestly noted that there was changes and synaptic bison. But synaptic python is not equivalent to synapses.

00:54:28:23 – 00:54:54:10
Speaker 1
It’s equivalent to synaptic vesicles. There are two different things. So in this study we published a couple of years ago, we did electron microscopy with more commentary, but not for synapse density. But looking at structures of synapses. And the vesicles are completely different. And Alzheimer’s disease versus controls, they’re pushed away from the active sound. There are less of them.

00:54:54:12 – 00:55:26:08
Speaker 1
And they correlate with the changes in mitochondria, suggesting that the big change is synapse dysfunction and synapse abnormality, not synapse loss. And this comes back to actually the same thing for neuronal loss. Bob Terry demonstrated that during the early 80s, late 70s that there was no correlation of neuronal loss to Alzheimer disease in cognitive change. That doesn’t mean that people have Alzheimer disease.

00:55:26:08 – 00:55:44:07
Speaker 1
Course they have more neurons loss, but it’s not correlated strongly with less correlated cognitive change. Correct. And no correlation plaques were weakly correlated. Tangles were somewhat correlated. And this snapped off this and was highly correlated.

00:55:44:09 – 00:55:48:17
Speaker 2
So it’s about the health of the neuron. It’s not the neuron being there or not there.

00:55:48:20 – 00:55:51:00
Speaker 1
That you got it. Exactly.

00:55:51:00 – 00:55:57:07
Speaker 2
And it’s started up with synapse being there or not there. It’s about the help of the synapse and the health care Act.

00:55:57:09 – 00:56:25:10
Speaker 1
Totally. In fact, we, Mark Smith and myself, who played a major role, Mark Smith was a close collaborator. Binh, who unfortunately died over a decade ago. We reckoned that the neurons were in the hibernated state, which now, in current vernacular, they call senescent cells. So this is more in the theoretical. Have we written anything like this? Close, but never exactly.

00:56:25:12 – 00:56:52:05
Speaker 1
We thought that the neurons. Well, I wrote something over two decades ago. I said, the neurons have a choice in death that people are always talking about neurons dying. But most of those ideas stem from studying cells that are more disposable. If you’re looking at liver cells, hepatocytes are pretty much near identical. So if you had the chance of the parasite becoming a tumor, you would rather it died.

00:56:52:07 – 00:57:18:20
Speaker 1
But in the case of a neuron, you really don’t want it to die because loss of a neuron has loss of function. And further mature neurons do not form tumors. It’s stem cells related to them. Some mature neurons are said like cells have a choice. They could be let’s die if we have a defect or let’s not die.

00:57:18:22 – 00:57:39:10
Speaker 1
And I think that that’s the way neurons are said. They’re said, don’t die, don’t die, don’t die. So don’t die has a consequence because the consequence is that you’ll have to move all of your metabolism to surviving, and you give up functioning.

00:57:39:12 – 00:57:41:16
Speaker 3
Now, is there data to show that these senescence.

00:57:41:16 – 00:57:44:20
Speaker 1
Services, there’s data for, I’m saying not so great.

00:57:45:01 – 00:57:46:16
Speaker 3
Can they come out of senescence?

00:57:46:18 – 00:57:55:13
Speaker 1
Where can I think that there is? But the current this isn’t my word, but others laws. People are trying to kill senescent cells.

00:57:55:15 – 00:58:03:11
Speaker 3
Certainly, because walking. Right. We want to we want people talking about fasting and getting rid of senescent cells throughout the body by basically starving them.

00:58:03:12 – 00:58:18:17
Speaker 1
Yeah, but think about this. Then again, if you’re dealing with skin cells or liver cells, that’s a good thing. How is that useful for neurons in the brain? Every time you lose neurons, you lose function.

00:58:18:19 – 00:58:26:20
Speaker 2
My brain is shifting. And how I’m imagining what we’re doing is essentially like resuscitation of the neurons. Is our goal.

00:58:26:22 – 00:58:58:12
Speaker 1
Correct. But but to do so, you have to understand why they went into the state. Right? Because my view is that they moved to a state where they are not going to die. They’re resisting. Of course they fail and they die, but they move to a state. And to address this type of problem, we studied Arctic squirrels. And why we did that is, Arctic squirrels in Alaska lowered their metabolism to essentially zero during the winter.

00:58:58:14 – 00:59:30:04
Speaker 1
They allow themselves to cool down to minus three. And during that time, we found that the neurons cannot be killed when they’re running around like normal ground squirrels. They’re like rats. The same thing. Neurons can die. So is that, you know, relevant, I think partially relevant. Number one, the squirrel does this during its whole life. We’re only doing this in study when people are post reproductive.

00:59:30:04 – 00:59:57:18
Speaker 1
There’s not a huge amount of selection. So I view that this is a change that’s occurring that’s related to programs when most of selection is pre reproductive period. Right. If you don’t if you don’t live past 20 or sometime like that, you’re not going to have any children. Your genes are not going to go forward. If you have a problem when you’re 55, the impact is much smaller.

00:59:57:20 – 01:00:20:14
Speaker 1
It’s not zero, but it’s not at the same level. So I view that using programs. So when you’re talking about this children, when is the time of greatest cell death and the brain childhood, there’s a lot of thing. Right. Because the neurons that don’t correct correctly have to die in that case after they die. So how does that play out in Alzheimer disease?

01:00:20:14 – 01:00:29:22
Speaker 1
I think we’re reusing a lot of programs that were important when they are evolutionarily really important, but we don’t see them that way.

01:00:30:00 – 01:00:36:23
Speaker 3
So candy senescent cells come back. And then I’ve had discussions with others who believe that’s number one.

01:00:37:05 – 01:01:12:02
Speaker 1
All of the cells in the brain, all of the parameter cells all showed the same change. So when I look at oxidative damage and the hippocampus or something like that, all of the neurons look alike, whether they have a tangle in them or not. And in fact, if they have a tangle, they have less oxidative damage. So if you’re going to try to remove the cells, you’re going to have the brain go to mush, which is what we argued in the idea of apoptosis, that the idea that apoptosis, classic apoptosis, was important in the brain.

01:01:12:04 – 01:01:26:15
Speaker 1
Mark Smith and I calculated that you’d rarely see it. The run of neuronal loss is so small, and apoptosis only usually considered to take less than a day. You should see like 1 in 10,000 cells showing this.

01:01:26:19 – 01:01:31:11
Speaker 3
So apoptosis is planned cell death. It’s a purposeful thing in the correct.

01:01:31:11 – 01:01:36:17
Speaker 1
And that doesn’t mean it doesn’t occur. But there’s no demonstration of it.

01:01:36:19 – 01:01:45:06
Speaker 3
So cells neurons that have tail tangles, can those become untangled or can the axon be fixed. So the cell becomes functional.

01:01:45:06 – 01:02:16:16
Speaker 1
Them. Well I don’t think we know that okay. I don’t think we know that. And even along that line, the tangle itself has even been less carefully analyzed than the plaque because the if you isolate tangles from the brain, which is not difficult to do, not to purity, but at least highly enriched, they have different chemical properties than the type of paired Hilco filaments that now everybody uses for their studies.

01:02:16:18 – 01:02:38:06
Speaker 1
The ones that are used for the studies are soluble in detergents. The ones that are in vivo are totally insoluble in almost everything. I mean, the only thing I found that got tremendous solution was, hi page like high sodium hydroxide or extremely strong protease treatment.

01:02:38:08 – 01:02:40:23
Speaker 2
So some of which are bound to convenience.

01:02:41:04 – 01:03:11:23
Speaker 1
What if there was a big transition in the 90s, early 90s in which Sharon Greenberg came up with an isolation technique for a filament that look quite similar to those making up neurofibrillary tangles, but it has a different properties chemically. Now, when we’ve analyzed plaques, okay, so tangles have never been really analyzed biochemically. I mean, everybody will disagree with that statement, but it’s true.

01:03:12:01 – 01:03:42:07
Speaker 1
The plaques also were super complicated because we did mass spectrometry analysis of the components of pure plaques. And they contain many, many different components other than just amyloid. So these are very complicated structures containing lots of other components, some of which probably are important, some of which are just happened to be randomly there. But how those interact with cells is probably far more complex.

01:03:42:09 – 01:03:50:11
Speaker 2
You mentioned that you’ve been at this for 50 years studying oxidative stress, that you are not a spring chicken. But I am curious.

01:03:50:11 – 01:03:52:13
Speaker 1
Don’t don’t go into that.

01:03:52:19 – 01:04:04:13
Speaker 2
Well, I’m curious with your experience and your research, with what you’ve learned, what are you doing personally to protect your own brain health and your body in general as you age?

01:04:04:15 – 01:04:11:13
Speaker 1
Oh, my wife says that I don’t have any of the advice I give to other people, but, well, I do, I do.

01:04:11:13 – 01:04:12:23
Speaker 2
What are your recommendations? What are you.

01:04:12:23 – 01:04:43:17
Speaker 1
Well, no, I will say I walk our dogs at least three miles a day. Okay, so that’s one now, is that a brisk walk? Well, we live in the hill country, so I’m going up and down hills. I take supplements, even though I know that supplements may not be that great for taking. Oh, a multivitamin, fish oil, vitamin D, I take the next year that’s related to ice.

01:04:43:19 – 01:05:13:19
Speaker 1
So it contains vitamin e and carotenoids and, what else? I try to keep myself non stressed. I think I do better than I used to do in driving. Meaning for life. I like my students. I love doing research. I love my family. So I at least come close to the four things. I don’t know if I go to the Bredesen level of 36 things.

01:05:13:22 – 01:05:16:14
Speaker 2
You know, I was surprised that you didn’t mention sleep is.

01:05:16:14 – 01:05:39:16
Speaker 1
Oh, I yeah, yeah, yeah. No, I do make an effort to sleep seven plus hours a night, usually eight. But I keep a little bit of erratic hours. I generally stay up past midnight and I wake up, I don’t know, around 730 or 8 during the summer. I can come in. Well, I did a webinar this morning at nine.

01:05:39:18 – 01:05:56:12
Speaker 1
So anyway, then that case, I came to work partly at 1030 or 11 because that was after that event. But anyway, I try to sleep every night, and in the past that wouldn’t have been true. I would have cut down. And I do agree that sleep is support.

01:05:56:13 – 01:06:06:10
Speaker 3
Based upon your reading of the research, what do you like as far as food? Both foods that are great for the brain and foods to avoid?

01:06:06:12 – 01:06:29:22
Speaker 1
Well, again, my wife wouldn’t agree. I drink wine, red wine, and I am Portuguese, so I only I try to only drink Portuguese red wine, olive oil, Portuguese olive oil of course fish. I probably eat fish. Under three, probably four days a week.

01:06:30:00 – 01:06:35:04
Speaker 2
Now I have fish conscious about which fish? I mean, you’ve studied the effect of metals on the daily.

01:06:35:06 – 01:07:04:14
Speaker 1
Well, metals are more complicated than having too much metals. It’s the same thing as oxidative stress is that you really don’t understand why they’re there. So, you know, some companies have tried to reduce metals as a therapeutic venture. I think the metals are publications in the past have dealt with the issues of amyloid beta binding, copper and redox suppressing copper can catalyze oxidative damage all by itself.

01:07:04:16 – 01:07:37:06
Speaker 1
When amyloid binds to it, it blocks that. Okay, we published that, but I didn’t like that answer. Okay, I thought it was incomplete. And why I thought it was incomplete is because that is a historical metric, a fact. And I was convinced that a catalytic effect could be more important. And why I thought so is we had published at the same time that the metals associated with plaques and tangles had Fisher Oxidase certificate.

01:07:37:06 – 01:08:11:06
Speaker 1
That is the ability to change ion redox state. And that’s usually an important element to controlling oxidative stress. So I thought at that point, which was the 1997, that it was related to iron, we published that and PNAS proceedings, the National Academy of Sciences, and we did everything to rule out copper at our understanding at that point. Not happy with that conclusion, I have tried to figure out how to do this study better, and we’ve done much more about it.

01:08:11:08 – 01:08:45:08
Speaker 1
So now we understood that the iron was not associated directly with the amyloid deposits, not bound directly. A lot of it was present as magnetite crystals. And we directly determined that magnetite crystals and that they had magnetic properties, they were not magnetic, but they were super paramagnetic. And then in the more recent studies over the last couple years, collaborating with Joanna Collingwood in the UK, we demonstrated directly the redox state of the metals.

01:08:45:08 – 01:09:10:23
Speaker 1
And this is something I was really obsessed with, well, at least for 20 years. The magnetic properties and the redox state. Why? Because knowing there were redox pairs would show that it was catalytic. So I wanted to understand if there was copper one and copper one is inherently unstable. I know that’s super esoteric, but in order to catalyze the reaction, you have to transfer electrons.

01:09:11:00 – 01:09:25:10
Speaker 1
So in those studies we found something way beyond that. So we found copper one we found copper two we find iron to iron three but we found the dominant form of the metals was metallic.

01:09:25:12 – 01:09:26:09
Speaker 2
Metallic.

01:09:26:11 – 01:09:59:08
Speaker 1
Metallic iron zero and copper zero. And why was that bizarre? Because neither has ever been determined in a human body. Prior to our studies. Ever. Not even close. Copper zero has been found in bacteria. Okay. Living in copper mines, as an example. But iron zero doesn’t exist on the Earth. Essentially. You know, iron rusts. So unless it’s exposed to oxygen.

01:09:59:14 – 01:10:30:11
Speaker 1
And here it was in a black and stable. So we confirmed this even our studies initially were in isolated plaques, but we confirmed the work in tissue that has never been treated or anything done in situ frozen sections with no chemical treatment. The metallic forms, tangles which we haven’t published do not have iron zero or copper zero. They have metals, but not in the same redox state.

01:10:30:11 – 01:10:33:10
Speaker 1
So it’s again specific.

01:10:33:12 – 01:10:35:13
Speaker 2
So you’re saying specific to a healthy cell.

01:10:35:18 – 01:10:38:01
Speaker 1
Is for CV to plaques.

01:10:38:03 – 01:10:40:00
Speaker 2
Oh to plaques not to tingles.

01:10:40:02 – 01:10:41:00
Speaker 1
Not to tangles.

01:10:41:01 – 01:10:41:17
Speaker 2
Fastening.

01:10:41:22 – 01:11:09:18
Speaker 1
And that piece isn’t published in fact isn’t even submitted. But so I view that as kind of a control. Yeah. In any case, it says that there’s some redox properties that are really quite unusual. You know, both that it forms and iron zero and it is stable because we do not take any special precautions to store them. And an oxygen free environment.

01:11:09:20 – 01:11:35:12
Speaker 1
So the specimens are exposed to air and, you know, iron exposed to air. In fact, iron filings will spontaneously combust when exposed to oxygen under some circumstances. You know, the only form of iron that was known to ancient man were meteorites. That’s how they made, you know, metals and swords. The few that were made to tell you how rare iron was.

01:11:35:13 – 01:12:00:05
Speaker 1
There are some ore deposits that apparently have metallic iron, but really, really rare. You know, the way man created iron was to burn it together with charcoal, right? So the charcoal pulls the option out. So it’s a not an easy reaction to happen. How does how does that happen in the human body? We have ideas. You know, reducing power.

01:12:00:05 – 01:12:19:12
Speaker 1
But I think it relates to mitochondria very much so. We’re has one of the main things we’re trying to understand. So if we’re asking these very basic questions how are we going to treat Alzheimer disease and cure it when we barely understand what the plaque is made of? Well, I mean, I understand less what the tangle is. Okay.

01:12:19:12 – 01:12:22:15
Speaker 1
Right? I don’t understand the role of metals.

01:12:22:17 – 01:12:27:03
Speaker 2
But as a matter of fact, I’ve got to ask you about mercury because there’s mercury. Yeah.

01:12:27:05 – 01:12:30:12
Speaker 1
Well, that’s the fishy issue. So I do eat swordfish.

01:12:30:18 – 01:12:42:10
Speaker 2
You do eat swordfish. We get it. Mind blown. Stop right there, doctor. George Perry, eat swordfish. Now, you’re not worried about Mercury because I know the ahi. So should I.

01:12:42:10 – 01:12:43:15
Speaker 1
Also eat out?

01:12:43:17 – 01:12:46:04
Speaker 2
Should I not be worried about mercury?

01:12:46:04 – 01:13:01:14
Speaker 1
And I don’t eat swordfish every day. But I probably eat swordfish once a month. I do eat fresh tuna. I’m not a big fan of canned tuna. I do eat salmon, canned and fresh. I Portuguese sardines.

01:13:01:19 – 01:13:05:16
Speaker 3
Yes. Sorry, I was about to have sardines I love so I mean sardines every day.

01:13:05:18 – 01:13:13:21
Speaker 1
Well, sardines are probably much safer since her lower in the food chain and you definitely should only eat Portuguese sardines.

01:13:13:23 – 01:13:20:17
Speaker 3
Portuguese, everything. We got olive oil and evidently red wine is neuroprotective from Portugal. Oh.

01:13:20:18 – 01:13:26:18
Speaker 1
Of course, of course, if you get tarragon National, it has a lot of red color.

01:13:26:20 – 01:13:35:16
Speaker 2
Amazing, don’t you, Perry? I can’t let you go without asking. What do you hope after? After you’re gone? What do you hope you’re like? Oh.

01:13:35:18 – 01:13:40:18
Speaker 1
Well, you’re already getting me dead.

01:13:40:20 – 01:13:51:21
Speaker 2
Well, you’re on the Think Well Age Well podcast. And so I want one of the conversations that we talked about, you know, part of part of aging well is dying well. And why do you want to be remembered for what is your.

01:13:52:00 – 01:13:53:19
Speaker 1
You mean in terms of science?

01:13:53:21 – 01:13:56:20
Speaker 2
Yes, in terms of science. And like, no.

01:13:56:22 – 01:14:29:01
Speaker 1
You know, I think in terms of Alzheimer’s, I think probably the most important thing when they do science is to have a lot of observations. You know, there’s always criticism of descriptive science. But actually I think that for the most part, the best you can do is to describe something and describe something. Well. So I would like to be remembered that I described a lot of things before other people and had insights before other people would I like to have had my work eventually led to a therapeutic or a cure?

01:14:29:01 – 01:15:07:00
Speaker 1
Of course, but I’m not sure that will happen. You know, I think that’s something hard to know whether it will happen. But in terms of my descriptions of oxidative stress, vascular changes, origin of plaques, I’m doing work together with Ralph Nixon. Now who’s come? I also had ideas about how plaques form, which everybody hated totally. And Doctor Nixon, who was at NYU, came up with an idea that’s similar to what I had different, but close enough that I can accept that it’s similar enough.

01:15:07:02 – 01:15:34:21
Speaker 1
And, maybe this time it will be accepted because there were other people that came up with the same idea after me. And, they met with even the worst reception than me. So one of the things that probably is the most, I think, beneficial or not beneficial, it’s interesting how some ideas take off and some ideas don’t, and it’s not rational.

01:15:34:23 – 01:16:03:03
Speaker 1
I’ve had ideas that people liked and they took off. That’s why I’m highly cited, and I’ve had other ideas that I think were equally good that no one liked, and they can never tell me why, which I think is, is a fault of science sometimes how I have ideas that people say, well, is clearly is wrong. And I said, well, if you present the wrong idea to me, I get super excited because then I can write a commentary about how stupid the person is.

01:16:03:05 – 01:16:35:09
Speaker 1
And I’ve done that, several times, and I get really excited about it when you instead just dismiss things. I think it’s really improper, so I don’t dismiss the damn, I sound important and further delay by the amyloid cascade. Initially, I thought it was reasonable. I mean, I adopt everybody’s ideas, then I look, how do they fit in with what I now from other people or myself?

01:16:35:11 – 01:17:00:03
Speaker 1
And I decide my own path. I think there’s too much people wanting to be self reinforced and science, and that is it’s not that much different than high school. The thought that in high school, you know, you had the people on the football team, you had the cheerleaders, you had the nerds, you had the weirdos.

01:17:00:05 – 01:17:03:08
Speaker 2
And and what group were you in?

01:17:03:10 – 01:17:27:00
Speaker 1
I don’t know, certainly not to football the cheerleaders, probably the nerds. I was certainly not in the popular group. And I see that in meetings. People want to be popular. By the way, I’m not against being popular, but I’m not willing to pay. Oh, yeah, it is useful to be popular. It’s useful to be rich. It’s useful to be attractive.

01:17:27:05 – 01:17:28:03
Speaker 3
They’re helpful things.

01:17:28:03 – 01:17:47:06
Speaker 1
All things. Yeah, but you know what? You can’t be all of them. They all have a cost. And whether I’m. I’d like it to be that I actually tried finding the truth. That’s what I tried all the time. To find things that would stand the test of time and be true.

01:17:47:08 – 01:17:49:20
Speaker 2
Regardless of their popularity.

01:17:49:22 – 01:18:06:08
Speaker 1
Popularity is a secondary feature, the secondary feature and unpopular among the people that count. To me anyway, and the other people that I’m not popular with. So what?

01:18:06:10 – 01:18:10:02
Speaker 2
Well, where in your fan club we like, you know.

01:18:10:04 – 01:18:12:15
Speaker 1
Oh, thank you very much.

01:18:12:17 – 01:18:35:19
Speaker 2
Doctor Perry. I just want to acknowledge how much you’ve contributed to my personal understanding of Alzheimer’s disease and my clinical work. And then, of course, to my profession, creating a venue where my work could be published. My research could be published. So I cannot thank you enough for that. And generally to your contributions to science and our understanding of the disease.

01:18:35:19 – 01:18:42:13
Speaker 2
So thank you. And thank you also for your time today. It’s really an honor and a privilege to have you here.

01:18:42:15 – 01:19:00:06
Speaker 3
You said that perfectly. Doctor Sanders said, thank you for for publishing my research. And thank you for questioning the status quo in science, which is, I think, what good science is. It’s questioning what is and, and, and for having such rigorous standards in your journal and for creating a journal. I had this running joke. People say, my doctor says there’s nothing to do about Alzheimer’s.

01:19:00:10 – 01:19:15:10
Speaker 3
I said, well, what do you think the Journal of Alzheimer’s is about? Do you think we just publish articles that says nothing to do and like, and every and every month is the same issue that there’s nothing to do about Alzheimer’s? Is that what you think we’re doing? So I love the journal that you created and I so appreciate that contribution.

01:19:15:15 – 01:19:46:12
Speaker 1
There’s lots you can do. There’s lots you can do even after you have the disease. You know, maybe the exercise and all this stuff is not going to be as effective. But there’s so much work which says that you can have an impact for families, for cost to society, and further to removing the stigmatism. Yes, because Alzheimer’s, even if you do all of these things and still likely to be a phase of life for many people.

01:19:46:14 – 01:20:06:00
Speaker 1
And what do you do? Do you wall people off, or do you figure out how to integrate them into the society as much as possible? And we did that for ancient societies, right? Grandparents and great grandparents that they were still living played an impact. And helping the families. They had a reason to be alive.

01:20:06:02 – 01:20:07:01
Speaker 2
Meaning.

01:20:07:03 – 01:20:32:11
Speaker 1
Meaning and we’ve removed a lot of that from modern society, and we probably can’t go back. But there can be new ways to do that. And all of those things can actually lower the cost to society. And I think that’s an important element of lowering the cost, because otherwise it’s going to be a tremendous burden, which it shouldn’t be, and we shouldn’t view it as a burden.

01:20:32:11 – 01:20:34:20
Speaker 1
If they were more integrated.

01:20:34:22 – 01:20:42:16
Speaker 2
And agree more. Well, you don’t forget to tell your family that we think you’re wonderful.

01:20:42:18 – 01:20:43:12
Speaker 3
We are. We probably them.

01:20:43:12 – 01:20:45:13
Speaker 2
After. We don’t need to call your wife and let her.

01:20:45:15 – 01:20:49:01
Speaker 1
Yes, you should call my wife or said their name. And I think.

01:20:49:02 – 01:20:52:20
Speaker 3
We can sing your praises. And then you can. You can tell her how,

01:20:52:22 – 01:20:54:06
Speaker 2
Why you’re late for dinner. Yes.

01:20:54:10 – 01:20:55:01
Speaker 3
Exactly.

01:20:55:01 – 01:21:03:15
Speaker 1
Yeah. No, I’ve been getting a few messages there. She usually calls me. I’d say it’s only a few minutes. She usually calls me around five. Why am I not leaving?

01:21:03:17 – 01:21:08:01
Speaker 2
And I. We can see the clock behind you. It’s 510 central time. Oh.

01:21:08:03 – 01:21:18:13
Speaker 1
Yes. Exactly. I have clocks everywhere. I’m tend not to be punctual, but I have. I’d see my phone, a clock. Right. Is there another one up there.

01:21:18:15 – 01:21:35:16
Speaker 2
That won’t be part of your legacy? But tell your wife you’re late to that hour today because we’re big fans, and we were hoping to extract some wisdom and, and just some of your experience from you because it’s so inspiring. It’s so hopeful. And, you’re just doing some incredible work. So thank you again for being here.

01:21:35:16 – 01:21:35:21
Speaker 2
Thank you.

01:21:35:21 – 01:21:36:07
Speaker 3
So much.

01:21:36:07 – 01:21:39:02
Speaker 1
Thank you very much, Heather. It’s great to meet both of you.

01:21:39:07 – 01:22:09:13
Speaker 2
Thank you so much for listening to the Think Well Eat Well podcast. If you enjoyed today’s conversation, please take a moment to subscribe, leave a review and share this episode with someone you care about. It’s one of the best ways to help others discover tools and inspiration for aging well. To stay connected, get bonus resources, and never miss an episode, head over to doctor Heather sanderson.com and join my email list.

01:22:09:15 – 01:22:13:22
Speaker 2
And till next time, keep thinking. Well, an 18 on purpose.