Ep 78: Dr. Rudy Tanzi - Alzheimer's Updates and Developments; What's New for 2025? (part 1)

Join BrainStorm host Meryl Comer as she kicks off 2025 with "Rockstar of Science" Dr. Rudy Tanzi, the pioneering Director of Genetics and Aging Research and Director of the McCance Center for Brain Health at Mass General Hospital. Dr. Tanzi delves into the new FDA-approved drugs, early cognitive blood tests, and why treating Alzheimer's should mirror our approach to heart disease by focusing on prevention long before symptoms appear. Drawing from his decades of research, Dr. Tanzi shares his vision for the future: a simple daily pill that could prevent Alzheimer's just like statins prevent heart disease. Whether you are concerned about brain health or fascinated by cutting-edge medical science, this episode offers hope and practical wisdom from one of the field's most influential voices. You don’t want to miss it!

Transcript

Dr. Rudy Tanzi (00:00):

So we do have blood tests. Now that can tell you quite accurately if you have amyloid accumulating in your brain. The reason why they're not covered by insurance or Medicare is because they're not actionable. Meaning if someone who doesn't have Alzheimer's disease symptoms at all said, Hey, I want to know if I already have amyloid. I heard from this guy Tanzi and others, that amyloid begins in the brain a decade or more before you might have any symptoms of cognitive impairment. I want to know. Well, the thing is, if they find out that they have amyloid, the drugs that have been approved to clear amyloid have not been approved for prevention. They've only been approved for treating the earliest stages of the disease.

Introduction (00:38):

Welcome to BrainStorm by UsAgainstAlzheimer's, a patient-centered nonprofit organization. Your host, Meryl Comer, is a co-founder 24 year caregiver and Emmy award-winning journalist and the author of the New York Times Bestseller, Slow Dancing With a Stranger.

Meryl Comer (00:55):

This is BrainStorm and I’m Meryl Comer. It's become an annual tradition to kick off a new year by checking in with our “Rockstar of Science” Dr. Rudy Tanzi, who discovered the first three Alzheimer's genes and has co-authored the New York Times bestsellers, Decoding Darkness, Super Brain, Super Genes, and The Healing Self. He is the Director of the Genetics and Aging Research Unit and Director of the McCance Center for Brain Health at Mass General Hospital. Dr. Tanzi is the Kennedy Professor of neurology at Harvard. Rudy, thank you for joining us.

Dr. Rudy Tanzi (01:34):

So great to be with you again, Meryl. It's going to be an amazing year in Alzheimer's, so look forward to talking about it.

Meryl Comer (01:40):

Rudy, over the past year, per your prediction, there has been first proof of concept that if you lower the amyloid, you can slow disease progression. Bring us up to date on the two monoclonal antibody drugs that have been approved by the FDA for early stage Alzheimer's disease.

Dr. Rudy Tanzi (01:58):

Leqembi and Kisunla, both of these are immunotherapies, so they're IV injected, maybe someday subcutaneous, but IV injected antibodies that target the amyloid. And when the amyloid is targeted by these antibodies in the brain, it triggers its breakdown. It triggers the clearance of the amyloid by cells in the brain that house cells called microglia. So the good news is they do clear amyloid. Well, the bad news is they're very expensive and they have safety issues. They can cause swelling in the brain and small hemorrhages. And in fact, the most common risk factor in Alzheimer's APOE4 in many places, if you have two copies of E four, one from mom and one from dad, you are denied this treatment because the risk in the a OE four carriers, especially two copies of the gene variant, are at higher risk for swelling and hemorrhage. So I think it's a great start, but we have to do better in two ways.

Dr. Rudy Tanzi (02:50):

One is we need to hit amyloid earlier. I always said to you, Meryl amyloid is to Alzheimer's disease as cholesterol is to heart disease. And just like the drugs we take today to manage cholesterol and stave off heart disease later on, we don't wait for symptoms of heart disease before you take a cholesterol drug. We're going to have to do the same thing for amyloid plaque. The amyloid starts to accumulate in the brain decades before disease symptoms and that's when you really need to hit it. But it was great that in the trials they treated the earliest stage patients who are just turning the corner from Alzheimer's pathology to Alzheimer's symptoms, you know, cognitive decline and showed they could slow down that cognitive decline. But ultimately we want to do much better. We want a prevention strategy. And so for that purpose, we're going to need similar drugs that clear amyloid or stop amyloid production, but they need to be used a decade or more in advance to prevent the disease rather than wait for the symptoms. And that's what I look forward to and I think we're going to be making great progress in that regard.

Meryl Comer (03:48):

Rudy, let's go where the field is when it comes to expensive new blood tests for Alzheimer's disease that have hit the market but are not yet covered by Medicare.

Dr. Rudy Tanzi (03:58):

So we do have blood tests. Now that can tell you quite accurately if you have amyloid accumulating in your brain, the reason why they're not covered by insurance or Medicare is because they're not actionable. Meaning if someone who doesn't have Alzheimer's disease symptoms at all said, Hey, I want to know if I already have amyloid. I heard from this guy Tanzi and others, that amyloid begins in the brain a decade or more before you might have any symptoms of cognitive impairment. I want to know. Well, the thing is, if they find out that they have amyloid, the drugs that have been approved to clear amyloid have not been approved for prevention. They've only been approved for treating the earliest stages of the disease, that very narrow window. So again, that's why I think we have to come up with safer, more affordable drugs to do this. There are some who would say it's still not worth paying for these biomarker tests because you can have amyloid without the disease and never get the disease.

Dr. Rudy Tanzi (04:49):

And to them, I would say it's a matter of time. Okay? If you have amyloid, it's like having high cholesterol. Some people might have high cholesterol, not treat it and not live long enough to have congestive heart failure. They might die from something else. Amyloid is the match. Amyloid lights, the fire of the tangles, the tau tangles that then propagate and spread in the brain. And over time, that starts to kill nerve cells and eventually that starts to trigger enough inflammation in the brain. Neuro inflammation, that's the wildfire, right? Amyloids to match tangles of the brush fires. You can live with those. Once you start that wildfire of neuroinflammation, there's 10 to a hundred times more so death. Then you start seeing the symptoms. So if you want to nip this in the bud, you hit amyloid early on, just like you hit cholesterol and heart disease. For those who are saying, well, but how about these people who had amyloid and then they died and then they didn't have Alzheimer's by the time they died. Genetics, lifestyle all dictate how fast you might go from the match to the wildfire. Just 'cause you escaped the wildfire when the match was lit. Doesn't mean that we roll the dice with everybody and say, yeah, you have some amyloid, but you know what? I bet you're not going to get the disease if you have safe enough drugs that are affordable enough. You prevent the disease.

Meryl Comer (06:06):

Rudy, are you concerned that the biomarker test may tag too many people with an inaccurate Alzheimer's diagnosis? That carries with it such stigma?

Dr. Rudy Tanzi (06:17):

If you tell somebody they have Alzheimer's disease, and let's say you say you don't have the clinical symptoms of Alzheimer's yet you can go do your job just fine and balance your checkbook just fine, but you have pathological or biological Alzheimer's disease, like someone might have a cell that's roguely dividing that's going to become a tumor and it's detected early on or a small tumor, there's no symptoms, right? We still say you have cancer. When I was growing up, there used to be the C word. We didn't say cancer. There was a stigma there too. We have to deal with this somehow. Maybe we don't call it Alzheimer's. When you have just the pathology brewing a decade or more before symptoms, you know, I like to call it biological Alzheimer's, but still the name Alzheimer's stigmatizes. It's like, oh, I might lose my job 'cause I have Alzheimer's.

Dr. Rudy Tanzi (07:02):

We have to figure out a way to do the nomenclature, the right way to de-stigmatize so we can tell people, and it's most important to do this. You have the biology going, you have the pathology brewing. You might not live long enough to get this disease. Your genetics and your lifestyle may allow you to stave it off even though you have amyloid. But we're not going to roll the dice. Just like if you have high cholesterol, we don't roll the dice. We bring your cholesterol down. We need to bring your amyloid down again. We're going to need safe and affordable drugs that can be used for a long time to do that. It's exactly what I'm dedicating all of my research to.

Meryl Comer (07:34):

There are dueling definitions in the global research community regarding exactly what should be the diagnostic criteria to redefine Alzheimer's disease. Is it purely biological or a combination of clinical and biological changes in the brain?

Dr. Rudy Tanzi (07:52):

Like myself, right? My dad died with a heart attack when I was 17. He was 45. My father's father died at 45 and he was 17, two generations in a row. So I saw a cardiologist when I was 29 years old. And I know my genetic risk factors and I deal with it. I'm well past 45 obviously, and so I keep my cholesterol low enough to keep myself out of trouble. Now, heart disease, until you had symptoms of heart disease, congestive heart failure, you can't walk up three stairs without huffing and puffing, right? We don't do that. Like I'm diagnosed because I have a little bit of plaque, a tiny bit of plaque. They say that's coronary artery disease. That's not a stigma. That's not congestive heart failure. I don't need a bypass. But knowing that I'm starting to form plaque on my arteries at my age and my sixties, well I deal with it.

Dr. Rudy Tanzi (08:42):

I keep my cholesterol low, I treat it pharmacologically. Somehow. We need to do the same for Alzheimer's disease, right? The thing is, we don't diagnose Alzheimer's disease until there are clinical symptoms. Even with mild cognitive impairment, the brain has already undergone enough deterioration and degeneration that if it was heart disease, you'd say somebody already had beginnings of congestive heart failure. We don't wait that long there to say, let's treat heart disease. We have to do the same thing for Alzheimer's. So if we have to rename it, fine, but the fact is this disease begins a decade or two or three before symptoms. And if calling it Alzheimer's makes one think, oh, this person has cognitive impairment, well no, they're not there yet. Let's just think new nomenclature that will get us around this problem. 'cause this problem shouldn't hold us back from early detection, early intervention.

Meryl Comer (09:30):

But Rudy wouldn't. You can see that there is a problem because what's happening with earlier diagnosis is the stigma trends younger and cuts people off in their prime professionally and personally. And the bottom line is that the general public is anxious, confused, and the primary care doctors are reluctant to diagnose

Dr. Rudy Tanzi (09:51):

You talking about a diagnosis of Alzheimer's disease based on cognitive impairment. Yes, that's just a challenge in the medical world of making a diagnosis that's accurate. You can have someone diagnosed with cognitive impairment that might be due to a vitamin deficiency. It could be a temporary delirium due to a urinary tract infection. It could be someone who's incredibly stressed out, who's not sleeping and suffering temporary memory problems. So this is why it's so important that the doctor you go to, preferably in this case, a neurologist or psychiatrist, psychologist, knows how to diagnose the disease differentially to rule out other potential reasons for cognitive problems that are not necessarily due to Alzheimer's disease.

Meryl Comer (10:33):

What would be your advice, Rudy, to those who have been diagnosed with Alzheimer's but are now skeptical about their own disease progression and say, well, maybe I better get rechecked.

Dr. Rudy Tanzi (10:45):

If you're feeling like you're made a comeback after a diagnosis, whether that diagnosis is accurate or not, then go back and have a new neuropsych exam. For sure. Clinical diagnosis of Alzheimer's based on asking questions to someone about their memory. It's not perfect. We've gotten better every decade. The accuracy rate in terms of detecting Alzheimer's is better. Differentiating Alzheimer's from other forms of dementia has gotten better, but it's not perfect. I've met people who told me, Hey, I thought I had Alzheimer's disease. And someone said, just get more sleep. And that did the trick. I couldn't find words and I couldn't keep track what I was doing because I was sprinting the candle on both ends and stressing out and getting two hours of sleep. You know what? Eight hours of sleep and all of a sudden you feel good again. That can happen. But I would say anybody who's worried about Alzheimer's shouldn't hesitate to go to the doctor. You know, meds out there that can help you. If you have the earliest stages of Alzheimer's and there's amyloid brewing, there are drugs now that can clear that amyloid. But if you think you've been misdiagnosed, for sure, go back and get it redone. It could have been cognitive impairment for a different reason. I look forward to a day where we will actually have primary prevention of Alzheimer's

Meryl Comer (11:51):

Help us out. What's the difference between primary and secondary prevention?

Dr. Rudy Tanzi (11:56):

Primary prevention means there's no pathology of Alzheimer's yet. There are no clinical symptoms obviously, and we want to turn down that amyloid production to a safe level. So if you have a genetic predisposition that says you're pretty high chances of getting amyloid and our drug is safe enough and affordable enough, you start taking that drug just like I did at 29 years old, 'cause of my family history of heart disease. I started statin, right? Cholesterol drug. So that would be the goal. Secondary prevention means amyloids already in your brain. The blood test shows that. Now let's clear it away. That's what these two new Alzheimer drugs that were approved to. And again, we need drugs that are safer and more affordable to do that. And you want to do that early enough before the amyloid causes too many problems. 'cause the amyloid is the match. It's triggering the tangles and the inflammation. So you want to hit that early. So the whole name of the game now is safe, affordable drugs that will merit early detection with blood tests to say it's time to start primary or secondary prevention based on genetics or biomarkers, and then nip this disease in the bud. Never let it become a problem end. This disease eradicated. It's doable and it's begun. We're marching onward right now. Rudy,

Meryl Comer (13:01):

Where are you in your research developing a small pill, not unlike a statin taken to protect against cardiovascular disease, it would help prevent Alzheimer's.

Dr. Rudy Tanzi (13:12):

Well, the little small pill I think you're talking about is the gamma secretase modulator or GSM. That's a drug that I've been developing now for over 20 years, and this is a drug that will hopefully safely turn down the production of the amyloid in the brain. Just like people who have high cholesterol, the drug they take usually will turn down the production of the cholesterol. It's been challenging in the drug industry to come up with something that will safely turn down amyloid production because the drugs that were tried so far over the past 20, 30 years weren't safe. My late colleague and my late best friend, Steve Wagner, and I had this idea, let's not hit the enzymes that make amyloid with a sledgehammer. Let's learn how to tweak them with the Juul a screwdriver so that they can still do their other jobs in the body and you don't have side effects. It's taken a long time. I've been very fortunate. The NIH through Francis Collins Neurotherapeutics Blueprint program has funded this program to a tune of 30 $40 million to cure Alzheimer's Fund has supported millions of dollars into this development. And finally, we were ready to go to the FDA to say, let's start a trial with a drug we have. So I started a company called ACTA Pharmaceuticals. I'm the founder, and of course I have equity in the company for disclosure. And ACTA licensed all of the intellectual property for Mass General for the gamma Secretase modulators.

Meryl Comer (14:32):

Rudy, the goal of prevention is to make individuals more proactive about their health and includes how we engage with our primary care doctors. What specific tests and results should we be tracking for our brain health?

Dr. Rudy Tanzi (14:46):

There's a blood test out there that can tell you if you have amyloid in your brain. I think the best one is from St. Louis is from a company that my close colleagues, Dave Holtzman and Randy Bateman started called C two N, letter C number two, letter N. Like you said, that blood test isn't covered yet by insurance or Medicare because it's not actionable. If you find out you have amyloid, there's not a drug you can take as someone who's asymptomatic or presymptomatic, they will stop it other than shield, you might ramp up shield, ramp up your vegan diet, exercise more, sleep more, et cetera. I tell people, look, you got to ask yourself, do you really want to know? You take this blood test and find out there's amyloid in your brain. You're not eligible for the two new approved drugs, which are only for the early stage Alzheimer's.

Dr. Rudy Tanzi (15:26):

Plus they have the safety issues. They're very expensive if you try to get 'em out of pocket. And I wouldn't recommend that either. You know, the stress that test could cause could actually lead to more inflammation than the amyloid would, and you might actually lose sleep and start binge eating junk food because you're stressed out. So you got to think, do I really want to know? Do I really want to have that test and is it going to stress me out until there's something I can do about it that will make my brain even more unhealthy? So you got to think about that.

Meryl Comer (15:53):

Let me ask you about the latest studies on the potential impact of Ozempic and Wegovy on the brain. Is it a lifestyle intervention for people with risk factors like diabetes or obesity, or are these drugs doing something more for the brain?

Dr. Rudy Tanzi (16:10):

They're dealing with addiction and appetite. They not only allow people to be less hungry and desire food less, but they seem to hit all levels of desire that gets out of hand. I would put it that way, not even at the state of addiction, but just craving, let's say it stops cravings. So it does have an effect on the brain. You know, I'm keeping close watch on these drugs because anything with that strong an effect on the general nature of humans, you know, cravings and desires. I think we do need to ask, what else are these drugs doing? I mean, certainly they've been a godsend for diabetes and for folks who are obese and need to lose weight, there was at least one phase two trial in Alzheimer's disease where although the effects on cognition were not remarkable in the small phase two study, there was less thinning of the brain for the people who took the drug versus the placebo. So that's a evolving story as to whether there'll be helpful for Alzheimer's through yet another mechanism we don't know about. So keep an eye on 'em. It's a remarkable medical story, that's for sure.

Meryl Comer (17:08):

Our guest, Dr. Rudy Tanzi, director of the Genetics and Aging Research Unit, and director of the McCat Center for Brain Health at Mass General Hospital and Kennedy, professor of Neurology at Harvard. In part two, we discuss prevention strategies, a brain care score, how predictive AI models are revolutionizing Alzheimer's research. And we invite chat GPT to offer some of its own rapid fire questions for Dr. Tenancy.

Dr. Rudy Tanzi (17:39):

I think we need other disciplines, especially engineering nanotechnology. Best thing I ever did in my own lab is collaborating and even hiring engineers who could bring the how question to what we're doing. We've spent so much time on what to do and where to do it, but how to get it done is engineering.

Meryl Comer (17:54):

That's it for this edition. I'm Meryl Comer. Thank you for brainstorming with us.

Speaker 2 (18:00):

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