Understanding the Power of New Blood Tests for Alzheimer’s Risk and Early Detection

[00:00:00] When you look inside the brains of people that have passed away from Alzheimer's, we see the accumulation of proteins in the brain. The challenge has been that up until recently, we haven't had a way to detect that before someone passed away. That many groups around the world have published have shown that in people that are beginning to develop Alzheimer's, so they don't really have full-blown dementia, but they may be five or ten years before that point,

[00:00:28] we can already detect the level of this protein increasing. If we wait until someone has Alzheimer's, so much damage in the brain has occurred, we are not going to be as effective in treating that person and slowing the disease and potentially reversing the disease.

[00:01:06] Alzheimer's is the diagnosis families fear most, and now there are blood tests that can detect it years before symptoms appear. But what do those tests actually really mean? And what should you do with the results once you've got them? And who should be getting them? So today on What I Tell My Family, Dr. Levine walks us through the new generation of Alzheimer's blood tests. No hype, no press release answers, just the honest reasoning he'd walk his own family through. I'm excited to hop into this episode with you. How are you doing, by the way, today? Great. Thank you so much. Yeah, great. Let's just dive right in.

[00:01:36] And let's kind of start with the basics. So a year ago, most people had never really heard of a plasma biomarker for Alzheimer's. But now it's getting a little bit more talked about. So what changed and why do you find that this moment is super significant in this area? Yeah. So I think the biggest change is that the FDA actually approved a blood test for the help in diagnosing people with Alzheimer's disease.

[00:02:03] So that led to New York Times, Wall Street Journal, CNN stories, all about this exciting development. And I think there's a couple of important concepts for people really to understand. So the first is what we mean when we say Alzheimer's disease and what we mean when we say dementia. So dementia is a term that means that people are having progressive loss of their ability to think correctly and to remember correctly.

[00:02:32] But that can be due to many diseases. So dementia is sort of an umbrella term for people that are having this kind of progressive difficulty with their thinking, their memory and their attention and other functions as well. The most common cause for dementia is Alzheimer's disease. And what we have known about Alzheimer's disease is that when you look inside the brains of people that have passed away from Alzheimer's,

[00:02:59] we see the accumulation of proteins in the brain. Some of those proteins occur within the nerves. And then some of those occur within the brain outside of the nerves. And that has led to a lot of excitement because we said, what if we could get rid of those proteins in the brain? Would it help restore the thinking of people with Alzheimer's disease?

[00:03:25] And the two important words to know are what those proteins are. So the first protein is called amyloid. And that's outside of the nerves in the brain. And then the second protein is called tau, which is T-A-U. And those are accumulations of proteins within the nerves. Sometimes you'll hear people describe them as plaques and tangles. So the plaques are the amyloid plaques that build up in the brain.

[00:03:53] And the tangles are the tau accumulations inside the nerves. So the challenge has been that up until recently, we haven't had a way to detect that before someone passed away. And so a tremendous amount of research has gone into this concept of what we call a biomarker. And so a biomarker is a way to look at something that's happening inside a person's body

[00:04:20] without having to wait until they pass away and we look at their brain. And so the big breakthrough has been this discovery of a protein called P-tau-217 or P-tau-217. And that's a blood test that we can now use commercially. We can detect it in the blood of people with Alzheimer's disease. And it has really improved our ability to detect the disease.

[00:04:46] But probably the most exciting thing is that recent data, really just even in the last 12 months that many groups around the world have published, have shown that in people that are beginning to develop Alzheimer's, so they don't really have full-blown dementia, but they may be five or 10 years before that point, we can already detect the level of this protein increasing. And so it becomes a risk factor to say that somebody has this protein

[00:05:15] and therefore they may be more likely to go on and develop Alzheimer's. So you just mentioned P-tau. Yes. And can you kind of walk us through some of the main tests like P-tau-217, NFL, amyloid ratios, and what is each one actually measuring within the brain? So what I'd like to explain to people about where we're moving in neurology

[00:05:41] is that we're about 30 or 40 years behind the cancer doctors. So if we think back, you know, 40, 50 years, if a woman had breast cancer, every woman got the same type of chemotherapy. And then the cancer doctors realized we could look for proteins on an individual person's cancer and being able to know what proteins are there allows us to say they're going to do better with this type of treatment or this type of treatment.

[00:06:11] And so that has been a revolution in the way that we've treated cancer patients. It's led to many more people being cured, much longer lifespans. And the word that we use is precision medicine. So not everyone with breast cancer gets the same chemotherapy. The same is really true, again, of dementia and even of Alzheimer's. Not everybody with Alzheimer's has the same type of problem.

[00:06:38] Not everybody with dementia has the same type of problem. This has probably led to a real inability for us to develop appropriate drugs. Because again, if you treated everybody with breast cancer with the same drug 50 years ago, we weren't very effective at treating that cancer. Now with precision medicine and cancer, we're very effective at treating many cancers. And we want to move in that direction with neurology.

[00:07:04] So there are a number of different ways to really think about this. The first is if you're having difficulty with your memory, if your thinking is not as good as we get older, what proteins are associated in your body with that problem? And so we mentioned P-tau, which is the tau protein. There's a protein called amyloid. There's a protein called TDP43. There's a protein called synuclein.

[00:07:32] And it's going to turn out, I believe, that individualizing these proteins and saying this is one person with memory loss that has this problem and this protein, and this is a different person with memory loss with a different type of protein, that's going to really lead to this concept of precision medicine. So in Alzheimer's disease, the two most common proteins to look for right now are tau, which are what we call tangles, and then amyloid, which we call plaques.

[00:08:00] And again, what has really evolved is the ability now to do that in living people. The most convenient way to do that is a blood test because blood tests are super simple. And this is now commercially available. We can also do it by looking at the spinal fluid. And then even more sophisticated, we can look at imaging of the brain, and we can now image amyloid accumulating in the brain.

[00:08:25] And so your doctor might choose one, all three, depending on the situation, to really try to be as confident as possible. So those two proteins, the tau and the amyloid, really allow us to get to that concept of which protein is building up in which patient. The other protein you mentioned, which I'm very interested in, is called NFL, like the football league. But it stands for neurofilament light chain.

[00:08:53] And that is another protein that's in each of our nerves. And so if the nerves are being damaged in some way, we can detect high levels of that protein that are leaking out of the nerves into the blood. And again, through blood tests or through spinal fluid tests, we can say this is a person who, for example, is developing memory problems, and we see that their nerves are dying because we see high levels of this NFL protein.

[00:09:23] So we really are evolving very quickly in these diseases to a place where we can say, this person is losing their memory because of an accumulation of protein tau. There's high levels of NFL suggesting that the disease is very active. Now let's think about ways to try to manage that and treat that, and then we can track these levels, and we can see if there's really been a change in what we're doing to the patient.

[00:09:49] So it is a very similar story. Again, if we think about cancer, we would treat someone's cancer with what we believe to be the right chemotherapy. And then in three or six months, say, did the cancer shrink? We're moving to that direction in neurology where we can really say, are we changing the course of a person's disease? So that's interesting, too, because exactly what you said about how cancer has been, I guess, more progressive in terms of things.

[00:10:17] So if a patient does or if a patient gets a positive P-tau 217 result, what does that mean exactly and what does that not mean? Yeah. So what it does not mean is that you definitely have Alzheimer's. And the way to think about the diagnosis of a disease is that we still rely on the clinical evaluation by a neurologist or by a neuropsychologist

[00:10:43] to say, yes, you're having progressive memory loss in these types of areas of your brain. And that's most consistent with Alzheimer's disease. That's still the clinical diagnosis. But we do know that having elevated levels of P-tau 217 in your blood is a risk factor for developing Alzheimer's disease over the next 5, 10 or 15 years.

[00:11:08] And so there have been large studies with tens of thousands of people really looking at this because we could go back to blood that's been stored 10 years ago or 20 years ago and say, OK, who had high P-tau 217? And then over the next 10 or 20 years, did that predict that they're going to get Alzheimer's? And so, again, it is not 100%, but it is a risk factor, right?

[00:11:34] It's similar to think about it if you had high cholesterol and you had diabetes. It doesn't mean that you're absolutely going to have a heart attack or a stroke, but it's a risk factor for a heart attack or a stroke. And therefore, we manage the cholesterol and the diabetes aggressively to prevent that from happening. And that's really the era that we're entering now, which is to say, if we wait until someone has Alzheimer's, so much damage in the brain has occurred.

[00:12:03] We are not going to be as effective in treating that person and slowing the disease and potentially reversing the disease. If I can get to someone and say, hey, you have a higher risk of developing Alzheimer's, and now we need to do these steps to slow the progression and hopefully reverse that, there's a much better chance if I do that 10, 20 years before their cognitive symptoms begin.

[00:12:28] So then with that being said, who should actually be asking their doctor for one of these tests right now to make sure that they're ahead of everything? Yeah. So it's a little bit of a personal approach to that. So I think the most likely scenario would be someone who's already beginning to develop a little bit of concern about their memory and their thinking.

[00:12:51] And then get to a primary care doctor, get to a neurologist, and the blood test becomes a way of saying, is what I'm seeing in my day-to-day life related to the early development of Alzheimer's? The catch being, again, that there are many other causes of dementia. So just because the P-TAU-217 is normal doesn't mean you don't have a different type of dementia. It's very specific for Alzheimer's disease.

[00:13:19] So really talking to a neurologist first and saying, is this clinical picture concerning for Alzheimer's? And if so, in my mind, the blood test is very indicated. Now, the second group of patients is really in large part where my preventative neurology practice has come in, which is to say, what about someone who has a parent who had Alzheimer's or is concerned about Alzheimer's,

[00:13:47] but isn't yet displaying any of the signs or symptoms? And in my mind, again, if we're going to be aggressive in terms of managing our health risks, then that's a very appropriate patient to have the blood test. Again, the blood test doesn't tell us that you have Alzheimer's today, but it does tell us that you are at higher risk of developing Alzheimer's. And then we can work on lifestyle modifications, other health issues that we can modify,

[00:14:16] things that we can do to try to slow that development over the next 5, 10, 15 years. So it's really those two groups. One are people with early symptoms where we want to know. And then the second might be people who want to be very proactive about their health and looking for risk factors. Again, very similar to the cancer story. So I went to my primary care physician, who's a concierge-type doctor,

[00:14:45] and he said, you don't have any signs of cancer, but here's a blood test that can detect 150 cancers long before they become a problem. And these types of blood tests are available even in the cancer space, not just for people who have cancers, but to try to detect it super early so that you could prevent the cancer from ever becoming life-threatening. Wow. So then what do you do with a positive result when there's no FDA-approved treatment

[00:15:13] to offer most patients now or even in the near future? Yeah. So the exciting thing is we do now have medications to slow and reverse the accumulation of amyloid. And so, again, in people that have memory issues, who have elevated levels of the P-Tau-217, we can put those people onto FDA-approved medications and try to reverse the effects in their brain.

[00:15:43] So that's why I say for symptomatic patients, it's very important because we now have some therapeutic options for them. Trials are underway now to say, what about the other group of patients? So the patients who don't have any cognitive loss, who have elevated Tau and amyloid in the brain, what if we put them on these treatments before they ever develop dementia? And so right now, those are not FDA-approved for what we call pre-symptomatic people.

[00:16:12] But we could be there in the next couple of years where we're really trying to use those medications, again, to prevent this from ever becoming a problem. In the meantime, it is a matter of kind of risk modification. So again, I'm going to turn 60 this year. My P-Tau-217 was normal. I did get it checked. But if it were abnormal, we would really want to focus on this concept of wellness.

[00:16:38] So we believe that improving sleep can help clear the proteins out of the brain. We know that social stimulation and mental stimulation are very important in delaying the progression. We know that diet and exercise are important. And it's also important to know that even in someone, for example, who's developing Alzheimer's disease, they can have other issues that cause problems with their thinking.

[00:17:05] So they could have vascular disease, diabetes, cholesterol, hormone issues. And so, again, in a person where we see a high P-Tau-217 without cognitive issues, it's really, again, to be proactive and to say, let's look at all the different things that we can do for this person to try to modify and slow the progression of the protein with the hope that eventually the pharmaceutical companies keep catch up

[00:17:33] and say, OK, now this is what you do for that patient and for that patient. So it's not sort of my grandmother's version of Alzheimer's, which is, oh, you have Alzheimer's. There's nothing we can do. Let us know when you need to go to a nursing home. My view of this is that we can be very proactive and really change the course of the disease today, even if we don't have the perfect drug treatments. Absolutely. That's great. I know even in my experience, and I'm sure most people listening and most people that you come across

[00:18:02] in practice kind of have that mental thought about it, about, oh, you know, you have Alzheimer's, you go to a nursing home. It didn't previously seem like there was so much that can be done, but it sounds like there's a lot more progressing that can be done, even if it's not perfect yet. But how do these blood tests compare to PET scans and spinal fluid tests? And when does each one really make the most sense? Yeah. So what's amazing about the P-TAU-217 test and really what led to the FDA approval

[00:18:31] is it's just about as good as the two other kind of a little more standard, much more expensive and invasive tests. So spinal fluid allows us to look at the fluid that circulates around the brain. And we always thought that's where you would be able to detect these proteins. We've known about that for a couple of decades, but patients don't love spinal taps, and it's a bit invasive. So, you know, really limits the utility of that test.

[00:19:00] The PET scan is a great test for Alzheimer's disease because, again, we can see the accumulation of the amyloid. So it's not even just a regular PET scan. It's what we call an amyloid PET scan. So we can actually visualize how much amyloid is in the brain. And the ability to do that really led to the FDA indication of these new medications because the new medications definitely lower and reverse the accumulation of the amyloid in the brain.

[00:19:29] Amyloid PET scans are very expensive and not so easy to acquire. So they're, you know, in New York City, there are places, but in many parts of the country, there may not be access to amyloid PET scans. So the blood test really becomes, you know, a few hundred dollar test to be able to say, do I need to worry or not? And then depending on the situation, the neurologist might say, oh, we need the amyloid PET scan anyway, or let's do a spinal fluid tap anyway.

[00:19:58] But as a screening tool, which is convenient, safe, cheap, the blood test is really revolutionizing the way we think about Alzheimer's. And APOE4 is in the mix for a lot of these patients. So do these blood tests tell you anything that genetic testing doesn't tell you or even vice versa? Yeah. So APOE4 is a genetic test, whereas P-tau is a protein test. And APOE4 is important.

[00:20:28] So the APOE is a gene that all of us have. We get one copy from our mom and one copy from our dad. The APOE gene comes essentially in four flavors, one, two, three, four. And four carries a higher risk of Alzheimer's disease. And if you have two copies of four, you have a significantly higher risk of Alzheimer's disease. So many families where you see multiple generations with Alzheimer's disease

[00:20:56] have what we call familial Alzheimer's disease. It's caused by a genetic change. And APOE4 is one of those genetic changes. So number one, if there's a strong family history, we often do genetic testing, which could include APOE4 but many other genes. APOE4 is one of the most common risk factors for the development of Alzheimer's. So again, some people with a family history might say, I'd like to know my APOE type.

[00:21:26] And if they were, you know, got a four from their mom and a four from their dad, again, it doesn't mean they're going to get Alzheimer's or that they have Alzheimer's, but it means that they're at higher risk of Alzheimer's. If the APOE types are not fours, then there's less risk. It's also an important fact to keep in mind that for people that are considering the new therapies, what we call the anti-amyloid therapies that have been approved by the FDA, we don't treat people that have APOE4.

[00:21:55] That's because there is a higher risk of side effects to those treatments. So if we diagnose somebody with Alzheimer's disease and we're considering the new treatments, we will sort of necessarily do the APOE testing because if they have APOE4, then they're not really a candidate for that type of testing because of the risk. So it is a genetic test. It is, again, just a risk factor. It doesn't mean that you have the disease, but it does mean, again,

[00:22:22] if you have two copies of E4, that someone is at higher risk of developing Alzheimer's. And then talking about families, I'm sure it's a difficult conversation to have with families when this happens. So can you kind of walk us through how you'd actually counsel a family after a positive test? And what does that conversation really look like in your office specifically? Yeah. So the counseling really depends, again, on the clinical stage of the patient.

[00:22:49] So if we take a patient who wants to be very proactive about their health, maybe has a concern for Alzheimer's where we find a positive P-Tau217 test, the counseling is really based on let's do what we can to modify your risk factors. That may be some medications. It might be changes in lifestyle. And then we can monitor them carefully. So we can look at these proteins over time. We can think about other types of imaging like the amyloid PET scan

[00:23:18] to see if the person is developing symptoms. So it's really this is a person that doesn't have the disease, but I am worried about this person. And so we're going to watch them more carefully. The other is the person that comes to see me, you know, usually with their family where there is some issues with their memory and where we get a positive test. And then the question becomes, let's talk about the FDA approved medications. And is that something that a person wants to take on? Because there is some risk.

[00:23:47] But we do believe it gets rid of the amyloid protein very well in the brain. If there aren't disease modifying therapies, there are medications that help with the symptoms of Alzheimer's disease. And so we can talk about those which are much cheaper and much safer. And then a lot of it is really counseling the patient and the family about what to expect. Do we have to think about changes in where they're living or getting help at home?

[00:24:14] And it is a it's a disease that affects, you know, the big village, right? The whole family. And it's just as much counseling the spouse and the children and the family about how to deal with this disease as it is counseling the patient. So we have a big team of people that really help with that. So social workers and nurses and exercise physiologists and nutritionists and all of these people really trying to provide advice

[00:24:42] to maintain a person's level of function at the highest possible degree, again, until we get better medications from the pharmaceutical companies. Absolutely. And speaking about that from I think this is something that's newer, but these tests are now being direct to consumer marketed. So someone can actually order these online. So I don't know much about this per se, but I can see good and the bad in that. So what's your concern?

[00:25:13] Yeah, I mean, so again, information is good and access is good. And as I said, these blood tests are now just a few hundred dollars. So they're they're, you know, in the reach of many people to be able to do. And so I don't necessarily think that it's a bad thing. I think the problem is, again, it's not a definitive diagnosis. And so if you're a patient that orders the test because you have memory problems

[00:25:38] and the PTAO 217 is normal, it doesn't mean that you don't have memory problems. It may just mean it's not Alzheimer's disease. But there are many other causes of memory problems. So then you need to see a neurologist to figure out why I have the memory problems. If you have memory problems and order the test and it's abnormal, well, then we have to have the big conversations about treatments and symptomatic treatments. And again, that sort of has to be guided through a neurologist.

[00:26:06] So as I started this podcast saying there's these really interesting parallels with cancer. Right. And so if a woman has a sister who has breast cancer, that woman may decide I want to get my genetic testing for the risk factors because I might have, let's say, a prophylactic mastectomy or even prophylactically take out my uterus and ovaries because I want to prevent

[00:26:30] those cancers if I have that genetic mutation, even though the person has no symptoms. But in the cancer world, we would never let that person get that genetic testing until they've had genetic counseling so that they understand before they choose to do the genetic test the significance of those results. And in a lot of ways, I feel like we need that now in the dementia space, that before you

[00:26:57] choose to get the blood test, you need to have a discussion with me or a neurologist to be able to say, OK, as you as you asked me in the beginning, what does the test mean and what does it not mean? Right. Those are both really important here. And what we don't want to happen is lots of people who are thinking completely normally find that they have abnormal blood tests and then changing their life and retiring early and doing all kinds of things that may not really be necessary.

[00:27:27] Right. And so the best case scenario is to at least have some conversation with a health care provider, like with the genetic counselors before the test and then make your informed decision about whether you want the test. And the concern with the direct to consumer testing is they don't offer that ability. Right. When I sit in my office, I'm going to say this is what we would learn from the test. These are the things we won't learn from the test.

[00:27:54] And then it's completely up to the patient to decide if they want the test. Absolutely. And then so with these tests and like you said, that these tests are, you know, in the hundreds of dollars range and it's accessible to more people and information, like you said, is good. But there's a lot more that goes into it. So let's say your own parent asked you whether they should get one of those tests. Right. What would you actually say if it was someone that was that close to you?

[00:28:21] Yeah. So I think it's worth it. I mean, I think it's worth it because it gives us information about trying to be proactive about your health. Now, again, if you're going to do all the proactive things about your health anyway, then you don't need the blood test. But for Americans and for me as an individual, sometimes knowing, oh, wait, I have a little issue and I should address this little

[00:28:45] issue aggressively. I think that provides a tremendous value. Now, there may be many doctors who say, well, it doesn't provide a tremendous value. But again, that's sort of my approach to taking care of people now is it's not just do we have a pharmaceutical agent that can reverse this? It's how do we improve all the different parts of your life so that we give you the best brain health we can for as long as we can? And we do know there are lots of ways for us to do that.

[00:29:15] But again, getting that little kick in the pants to say, yes, we need to focus on this with you now. I find value in that. Yeah. Then with all these, you know, the way that technology is evolving and changing. And like you said, even over the last few years, there's been so much change. Where do you think that technology headed in the next, let's say, maybe two or three years is heading? And would you really make more or less or what would make you more or less likely to order these tests for every patient,

[00:29:43] let's say, over the age of 60? Yeah. So I think where we're heading is to get away from the concept of Alzheimer's disease, because even within that concept, there are very different types of people. Again, just like there are very different types of breast cancers, even though they're all breast cancers. So I think where we're going to head to is moving away from the concept of a label,

[00:30:07] but to say, OK, this is a person who's having progressive memory issues. The progressive memory issues are associated with these proteins building up inside their brain. We know that's bad. We have these measures of how much damage it's causing to the brain, which could be, again, blood tests like the neurofilament light chain or imaging tests like the amyloid test. And then now let's target that individual picture as opposed to just labeling them all as the same.

[00:30:35] And I think we've probably been unsuccessful because we haven't been able to say this patient has real this group of issues and this patient has this group of issues. And we just lump them all together as Alzheimer's. We treat them all with the same medication and we haven't been successful. And so where we're headed, I think, for sure, is this concept of personalized medicine.

[00:30:59] These are your risk factors. And then sitting down with doctors like me and saying, OK, how do I modify those risk factors? Again, no different than if you had high cholesterol and diabetes, we would modify those risk factors to prevent something bad from happening. In neurology, we're just getting to the place of being able to measure that, right? We know we can measure cholesterol. We know we can measure your glucose. We're just entering the era in neurology of being able to say, I can measure this

[00:31:27] in the brain, in the nerves, in the skin, in the spinal fluid and really get the right answer for each patient. It sounds like the new Alzheimer's blood tests are here and there's so much change. And I think, I mean, I learned so much. I'm still kind of digesting everything that you said. So it's so important to talk about this, especially like you said, people talk about cancer a lot and even, for example, breast cancer, people kind of group that together without knowing that there are different

[00:31:55] types of breast cancer. Like there's just so much more detail and things that a lot of people don't know, like even including myself. So before we wrap up the second episode, is there anything that you want to add or any final thoughts that maybe you didn't get to convey yet today? No, I think that the take home message really is it's not our grandparents' memory issues anymore. And we can be very proactive and we can be proactive in treating patients once they have symptoms.

[00:32:24] And we can be proactive in trying to diagnose these conditions years before they cause real problems. And so speaking with your doctors, your neurologists, and talking about whether that's appropriate for you, I think is the right step these days. And the new Alzheimer's tests are here. And as Dr. Levine explained, and as we learned through this episode, really knowing how to read them is just as important as ordering them. And if you found this

[00:32:50] useful, share with someone who's been worrying about their own risk or their parents or really anyone that they know. And in two weeks, the APOE4 conversation, the genetics question, most doctors won't answer honestly. And what Dr. Levine would tell his own family if they came back with a copy or two. So make sure you follow, subscribe and share this episode with anyone that can really benefit from it. And I can't wait to speak with you soon. Have a great rest of your day. And I can't wait for the next episode.