Understanding New Blood Tests for Alzheimer’s Disease

Podcast Transcript

Neuro Pathways Podcast Series

Release Date: February 15, 2026
Expiration Date: February 14, 2027

Estimated Time of Completion:  30 minutes

Understanding New Blood Test for Alzheimer’s Disease
Jagan Pillai, MD, PhD

Description
Each podcast in the Neurological Institute series provides a brief, review of management strategies related to the topic.

Learning Objectives

• Review up to date and clinically pertinent topics related to neurological disease
• Discuss advances in the field of neurological diseases
• Describe options for the treatment and care of various neurological disease

Target Audience

Physicians and Advanced Practice providers in Family Practice, Internal Medicine & Subspecialties, Neurology, Nursing, Pediatrics, Psychology/Psychiatry, Radiology as well as Professors, Researchers, and Students.

ACCREDITATION

In support of improving patient care, Cleveland Clinic Center for Continuing Education is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

CREDIT DESIGNATION

• American Medical Association (AMA)
  Cleveland Clinic Center for Continuing Education designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
  
  Participants claiming CME credit from this activity may submit the credit hours to the American Osteopathic Association for Category 2 credit.

• American Nurses Credentialing Center (ANCC)
  Cleveland Clinic Center for Continuing Education designates this enduring material for a maximum of 0.50 ANCC contact hours.

• Certificate of Participation
  A certificate of participation will be provided to other health care professionals for requesting credits in accordance with their professional boards and/or associations.

• American Board of Surgery (ABS)
  Successful completion of this CME activity enables the learner to earn credit toward the CME requirements of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider's responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit.
  
  Credit will be reported within 30 days of claiming credit.

Podcast Series Director

Andreas Alexopoulos, MD, MPH
Epilepsy Center

Additional Planner/Reviewer

Ari Newman, BSN

Faculty

Jagan Pillai, MD, PhD
Center for Brain Health

Host

Glen Stevens, DO, PhD
Cleveland Clinic Brain Tumor and Neuro-Oncology Center

Agenda

Understanding New Blood Test for Alzheimer’s Disease
Jagan Pillai, MD, PhD

Disclosures

In accordance with the Standards for Integrity and Independence issued by the Accreditation Council for Continuing Medical Education (ACCME), The Cleveland Clinic Center for Continuing Education mitigates all relevant conflicts of interest to ensure CME activities are free of commercial bias.

The following faculty have indicated that they may have a relationship, which in the context of their presentation(s), could be perceived as a potential conflict of interest:

Glen Stevens, DO, PhD

DynaMed Consulting

All other individuals have indicated no relationship which, in the context of their involvement, could be perceived as a potential conflict of interest.

CME Disclaimer

The information in this educational activity is provided for general medical education purposes only and is not meant to substitute for the independent medical judgment of a physician relative to diagnostic and treatment options of a specific patient's medical condition. The viewpoints expressed in this CME activity are those of the authors/faculty. They do not represent an endorsement by The Cleveland Clinic Foundation. In no event will The Cleveland Clinic Foundation be liable for any decision made or action taken in reliance upon the information provided through this CME activity.

HOW TO OBTAIN AMA PRA Category 1 Credits™, ANCC Contact Hours, OR CERTIFICATE OF PARTICIPATION:

Go to: Neuro Pathways Podcast February 15, 2026 to log into myCME and begin the activity evaluation and print your certificate If you need assistance, contact the CME office at myCME@ccf.org.

Copyright ©2026 The Cleveland Clinic Foundation. All Rights Reserved.

Introduction: Neuro Pathways: A Cleveland Clinic podcast exploring the latest research discoveries and clinical advances in the fields of neurology, neurosurgery, neuro rehab, and psychiatry.

Glen Stevens, DO, PhD: Blood tests for Alzheimer's disease are transforming how we approach, diagnose, and care for patients, bringing new possibilities for early detection, clarity in complex cases and practical tools for clinicians across specialties.

In this episode, we'll discuss the evolution of these tests, explore who should be considered for blood-based screening and break down how to interpret results in real-world practice.

I'm your host, Glen Stevens, neurologist, neuro-oncologist in Cleveland Clinic's Neurological Institute. And joining me for today's conversation is Dr. Jagan Pillai. Dr. Pillai is a behavioral neurologist and director of Cleveland Clinic's Center for Brain Health. He also leads the National Institute on Aging's Cleveland Alzheimer's Disease Research Center.

Jagan, welcome to Neuro Pathways.

Jagan Pillai, MD, PhD: Well, thank you for having me, Glen.

Glen Stevens, DO, PhD: So why don't we start by having you introduce yourself, your background training, and what you do at the Cleveland Clinic?

Jagan Pillai, MD, PhD: I'm a behavioral neurologist. So, people like me evaluate people with any cognitive concerns and problems, try to give a point of context as to why this is happening and help provide ways to manage them. And recently, we are also able to offer a lot of impactful therapies for some of our patients. I joined this field because I'm fascinated by the brain. That's why I became a neurologist. And being a neurologist, I've been trying to understand and help people with how their brain functions and find ways to preserve it has always been my passion. And that's got me into the field and into this kind of work I'm doing right now. I decided to go down this field not in a straightforward way. I thought I was probably going to be an epileptologist or a stroke doctor like most neurology residents.

But once I got to know this field and the kind of questions and the real dynamism in the field from how it's gone in the last two decades, I've been part of this journey and I've been riding this wave and I really enjoy it. My dad is an engineer and actually used to make rockets, so it's so far away from what he was doing. But I like the experience of finding new things, something I got from him. So, I was born in India and I came here for my residency and subsequent training. I joined the Cleveland Clinic about 14 years ago, and here I am.

Glen Stevens, DO, PhD: Well, we're happy to have you here and appreciate all you do. And of course, as I'm getting older, I'm going to appreciate even more what you do.

Jagan Pillai, MD, PhD: Well, it's something that all of us have to wrestle with, just like we wrestle with puberty.

Glen Stevens, DO, PhD: So, let's just give a broad definition. What is Alzheimer's disease so that everybody's on the same page and how's it been classically diagnosed?

Jagan Pillai, MD, PhD: That's a great question. That's one of the first things patients ask, "Do I have Alzheimer's disease? Do I have dementia?" So we use the word Alzheimer's disease specifically in specific context, but we use the word dementia more of a clinical syndrome to identify people who have changes going on in the brain because of which they're not able to take care of themselves independently in their daily routine. One of the causes and the most common cause of dementia is Alzheimer's disease, which is a neurodegenerative disease. For decades, Alzheimer's disease was something you, the clinician might make just by seeing the patient and seeing there's a deterioration function. They might say, "Well, you have Alzheimer's disease or Alzheimer's disease dementia." Then it became the question that you have to wait autopsy if the person has died to see if the person really has Alzheimer's disease.

Things changed in the last 15 years or so when we started having biomarkers so we can actually measure something in the patient to see if there's Alzheimer's disease changes that are specifically related to amyloid protein or amyloid plot related changes going on in the brain or tau related protein changes are going on. And what's so dramatic has been that previously these biomarkers were evaluated by very expensive tests like PET scans and CSF testing after lumbar puncture. And what has happened now and that's causing a lot of interest in the field is the availability of blood tests for measuring these proteins related to amyloid and tau.

Glen Stevens, DO, PhD: Again, just for background, tell us a little bit about what amyloid plaques and tau tangles are and why they're a problem. What's the protein doing? Why is it causing a problem or the thought?

Jagan Pillai, MD, PhD: When Dr. Alzheimer's initially described changes going on in the brain in somebody in mid '50s, he found out some aggregations of proteins and of two kinds. One is called plaques and second called tangles. Over a period of time through protein biochemistry, we found out that the plaques are made of the amyloid or beta amyloid pleated sheets. And the thought is that these beta amyloid pleated sheets build up over time, but in some people they accelerate and cause subsequent secondary damage to the neurons, the general health of the brain functioning and related to damage called the tau protein that is measured as a neurofibrillary tangle burden in the brain. Now, these proteins can spill out into the spinal fluid and the blood, and now we have ways to measure that.

Glen Stevens, DO, PhD: Are the majority of patients still getting PET scans and CSF, or are you seeing a significant change already?

Jagan Pillai, MD, PhD: That's a good question because there is a lot of interest in the blood tests and it has clearly shifted our understanding, but they're not still at a point to make a final definitive diagnosis. So, blood tests make... They're great tools that have been used in the right context to help narrow down the possibilities, but still before initiating treatment to remove amyloid plaques, for example, that is now currently available, you still have to go through an amyloid PET or a CSF evaluation to confirm what the blood tests show.

Glen Stevens, DO, PhD: My guess is you're going to see more and more patients coming to you with a blood test that haven't had anything else done, and then you're going to have to do the work on the other side.

Jagan Pillai, MD, PhD: That is correct. Actually, that is one of our huge challenges because I think the general word in the street is that there's a blood test for Alzheimer's disease, but not a lot of context around how best to use it, on whom to use it, how to interpret it, and how to best follow up. So, a lot of people who should not be getting the blood test in the first place could be getting these tests. And that's one of the concerns the field is really wrestling with.

Glen Stevens, DO, PhD: So, educate us on the blood test and what is it measuring and what are we looking for?

Jagan Pillai, MD, PhD: So, as you really lay the groundwork, I mean, there are two key proteins that are measured, the amyloid protein, beta amyloid protein and the tau protein. And these proteins come in different forms. So, there are different kinds of blood tests that measure different versions of the protein. So, it could be amyloid beta 42, amyloid beta 40 and phosphorylated tau, that's a P tau, 217, 181, 231, things like that. So, there are a lot of different varieties of these proteins that can be measured and the combination might differ in different companies, but the interpretation of that is usually determined by thresholds that the company provides. And then the clinician has to make clinical judgment, what that means for their specific patient. So clinical judgment is still paramount.

Glen Stevens, DO, PhD: And the first FDA approved blood test, and maybe I missed the date. I thought it was somewhere around May of this year.

Jagan Pillai, MD, PhD: Yeah, you're right. The blood test was approved in May of this year. And since then, I think last month they approved a second blood test. So, there are now two blood tests that are very distinct. There's FDA approved.

Glen Stevens, DO, PhD: Okay. Do you want to discuss those?

Jagan Pillai, MD, PhD: Sure. The one that was approved in May is by a company called Fujirebio Diagnostics' LumiPulse. It measures the ratio of phosphorylated tau 217 to beta amyloid 142. This is approved for patients who are 50 years and older, and it's only useful in a memory care setting. So, somebody should have a clearly documented cognitive impairment and a history of cognitive decline. And then this test can be used to assess the probability that underlying cause could be Alzheimer's disease. And if so, then they need additional testing, as I mentioned. The second test that was approved is by a different company called Roche. It's phosphorylated tau 181. And the FDA in this case has approved it for general wider use, but the field is trying to decide what that actually means in clinical practice.

Glen Stevens, DO, PhD: And it uses a ratio. Do both of them use a ratio?

Jagan Pillai, MD, PhD: The second one is a phosphorylated tau 181, and the first one is a ratio.

Glen Stevens, DO, PhD: And remind me, my recollection was the CSF will also look at a ratio or does it do both?

Jagan Pillai, MD, PhD: That is correct. I mean, the amyloid protein, when it builds up in the brain, it drops in the CSF and the plasma, but the amyloid protein is a very tricky protein to measure. It gets stuck in different methods of collection, very sensitive medical comorbidities. So, we use the ratio of amyloid protein to phosphorylated protein. We stabilize that number so we can standardize these much more widely.

Glen Stevens, DO, PhD: I mean, you had mentioned that patients need to have some sort of cognitive related problem to get the testing done, but it makes one wonder how long it will take that you can just go on your computer and go to a website and just order a kit and send off the test. I mean, this is how things move.

Jagan Pillai, MD, PhD: I mean, the question is, do you want a number, or do you want an answer? If you want a number, you can go to the website, as I said, and it'll give you a kit, it'll give you a number, but how does that really specifically mean in your context, in your life as you're trying to make a decision? That's where you need clinical judgment and expertise in interpreting that.

Glen Stevens, DO, PhD: And I know it's been a very short period of time. How do you see the blood test influencing or affecting your practice?

Jagan Pillai, MD, PhD: I think in two ways. One is a lot of conversations about this. So, the people are more excited and are wanting to get a cognitive assessment now because it's up in the front of their minds. Well, there's a blood test, maybe I have a concern, maybe I can get it checked out. So we're getting a lot more demand for people getting, wanting assessments. The second thing it is shifting is people who should not be getting these tests also are getting them. So, people who are completely normal, who might have a family history of Alzheimer's disease or anxious and want to get a test, they may do the test and get a result, which is not appropriate for them. So, then they may get a false positive test and they're struggling with what that means for them.

Glen Stevens, DO, PhD: Do they have any idea of when a test would be positive in the average time to develop the disorder or it's not on a ratio you can't just look and say it's this number on average, it would take 25 years?

Jagan Pillai, MD, PhD: That's a great question. So, one of the things that people are not generally aware of is that you don't wake up with Alzheimer's disease like a stroke. So it's a slow process happening in the body over a period of time. And now the estimate is that before you have clinical symptoms, some of the changes are going on 15, 20 years before. And so, there is a phase of Alzheimer's disease before the onset of symptoms that's called preclinical Alzheimer's disease where a person is cognitively completely normal. And if such a person were to do these blood tests, it will show up as positive. But we don't know if that person could develop symptoms or may not develop symptoms or might develop symptoms in the next five, 10, 15 years. So, the question is, what are you going to do with this positive test in this population? So that's where the need is to only do this test when there's clearly documented cognitive impairment.

Glen Stevens, DO, PhD: So, your message to primary care physicians out there, geriatricians, general neurologists about patient, I come in to see my primary care and they ask how I'm doing. I say, "I'm okay. I think I'm doing fine. I can't remember names quite as good as I used to." What's your recommendation for them?

Jagan Pillai, MD, PhD: Well, I think as a clinician, assess the clinical context. I mean, is this person right now having a clear decline from the previous baseline? Is that affecting the functional level at some point? Are there other clinical contexts? Is there a medical problem going on? Are they under a lot of stress? Is this depression? Do they have a sleep problem? Are they taking some medications that are causing cognitive side effects? And those things are front and center for any evaluation. Then once you do that, then rule out variable causes like is there a vitamin deficiency type or problem? Maybe they have a stroke. I mean, once you do all these things and then you come to the point that, well, there's nothing else going on. There's a clear memory deficit and that is declining. At that point, maybe a blood test may be helpful.

And even in that blood test, if it is a negative test, that's more helpful than a positive test. If a person who goes with this high symptoms gets negative, then you are looking for other causes, maybe they have a non-Alzheimer's related condition, maybe another degenerative disease or maybe another stroke related change or other something you're missing. If it is positive, then they need to see a specialist to really understand if it is truly Alzheimer's disease.

Glen Stevens, DO, PhD: Yeah. And I guess if they're symptomatic and it's negative, it's not exactly time to celebrate.

Jagan Pillai, MD, PhD: Well, maybe it's a treatable problem. I mean, you're doing this test in the first place because there was a problem, so you need to solve the problem.

Glen Stevens, DO, PhD: So are groups trying to come up with a criteria more than just, "Hey, my memory's not so good." Are they trying to develop criteria or is that just in the, we're thinking about it stage?

Jagan Pillai, MD, PhD: Well, right now, I mean, there's no specific criteria except the ones I am saying they're giving a lot more leeway to clinicians to make the right decision. And the best way that clinicians can make the right decision is getting educated. And that's why I really am here to make sure the word gets around.

Glen Stevens, DO, PhD: So, I come to see you, I'm having some memory related problems. You of course do a full exam on me, take a good history, maybe do a little cognitive testing on me to see how I'm doing. The blood test is negative. You look for all the treatable other types of disorders, don't find anything. What do I do with that then?

Jagan Pillai, MD, PhD: Well, your blood test is negative, but again, there are conditions where the blood test is still negative because you're still at the borderline level. So, if your clinical story is very concerning for Alzheimer's disease, despite the blood test negative, you would still go ahead and do additional confirmative testing, like a PET scan or CSF testing.

Glen Stevens, DO, PhD: Okay. Any data on the two tests that are out there in terms of sensitivity specificity together independently? Do we know?

Jagan Pillai, MD, PhD: I think one of the things, maybe it's true in a lot of different fields, is that many of these tests are developing specialized cohorts of people and mostly research cohorts, and it has not been widely used in the real world, real populations. So, the sensitivity specificity might change depending on the kind of population you're using it on. So that's one of the things that's not yet clear. So, the numbers of specificity of these tests that are FDA approved are over 95%, but how is it going to play out in the community when everybody is not having a clear story? And the prior probability of having Alzheimer's disease is one in 10 and over people over the age of 65. And that's really unclear right now. And there's a lot of discussion around that.

Glen Stevens, DO, PhD: So, I come see you have had a bit of nothing significant, but a bit of memory concern. I have a test that's positive. Are you going to do a PET on me? Do I get an LP? Is a history good enough?

Jagan Pillai, MD, PhD: I mean, if a person has a memory problem that's documented and that's objectively true and the blood test is positive, then you would have a follow-up PET scan or a CSF testing. If the patient wants to take it that direction, if the patient says, "I don't want to do additional testing, I don't want new medications, I just want to know what is my prior risk and manage it that way." Then no additional tests are needed. But if the patient insists that these are the steps they would like to do because they want to know these things to take this down a specific road of treatment plan based on that, then we will do those tests.

Glen Stevens, DO, PhD: Do you know how expensive the tests are?

Jagan Pillai, MD, PhD: The blood tests?

Glen Stevens, DO, PhD: Yeah, the blood tests.

Jagan Pillai, MD, PhD: So currently, they are not covered by insurance.

Glen Stevens, DO, PhD: Okay.

Jagan Pillai, MD, PhD: So it's variable depending on the specific company you go to. So, the range can vary somewhere in the hundreds to 800, $2,000, depending on who's doing it. And there is a lot of interest in legislation to make this actually covered by Medicare and at that time things will change again.

Glen Stevens, DO, PhD: I was going to ask you and not hold you to it, but do you think they will be covered? I would assume at some point down the road they would.

Jagan Pillai, MD, PhD: There's a lot of groundswell interest in getting it covered.

Glen Stevens, DO, PhD: And again, I won't hold you to this, but a year from now, will there be five tests?

Jagan Pillai, MD, PhD: Very likely. What we are likely to see is that the blood tests are going to get more accurate. I mean, maybe we might have a panel of blood tests that target specific trajectories. I mean, right now, as I said, when you have a blood test, you don't know what this means for you in five years. Is it going to progress or not? You don't have those. It's a yes or no answer, but it doesn't tell you what does it mean in terms of progression. I think we will start having those kinds of tests coming soon, next five to 10 years.

Glen Stevens, DO, PhD: I think the bad news for you is that you're going to have to start working Saturdays with all these new patients that are coming in.

Jagan Pillai, MD, PhD: Well, when it's already happening.

Glen Stevens, DO, PhD: What advice do you give to people out there that are going to be seeing these patients with the blood test? I guess just do the good clinical work you're normally doing, I guess, right?

Jagan Pillai, MD, PhD: I think if you have a positive blood test and symptoms that are very consistent Alzheimer's disease, then you should be referring that to a specialist. If it's a negative test and then the symptoms are unclear, borderline, then again, there is a role for a specialist, but if it's a negative test and the symptoms are stable, then just monitor management primary care. But the overarching thing is that you should be ordering the test after a clear cognitive evaluation showing there's a clear deficit and other things have been ruled out before testing the person.

Glen Stevens, DO, PhD: And any concerns or pitfalls with the tests other than what you mentioned of asymptomatic people getting the testing done?

Jagan Pillai, MD, PhD: Well, the pitfalls is that there are a lot of companies offering this test, and so there may be difference in quality of the test. So, whenever we think of a test, you think of a positive and negative, but there's a huge role of intermediate. And so, there's a line drawn and there's a line on the sand determining where the intermediate and all those things are and how to interpret that, how to make this meaningful for the patients and families so they're not left in limbo. I mean, it's a huge discussion. So, I think clinicians should be aware of that rather before ordering tests. So, it's not part of the general routine test like ordering a thyroid function test, but it's something that has to be carefully considered, thought, and intentionally done and knowing what you're going to do that you get that result.

Glen Stevens, DO, PhD: I can imagine a family coming into your office, four kids and a parent that is positive and all the kids want to get tested. I just imagine this is going to happen.

Jagan Pillai, MD, PhD: That's definitely something going on in people's thoughts. Yeah.

Glen Stevens, DO, PhD: So, where's the field going? This is all quite exciting, although obviously a lot of difficult things to discuss, but where are we going from here?

Jagan Pillai, MD, PhD: Well, I think positive. The field is very dynamic. It has been the most dynamic after a long period of building up steam. And we are now starting to see outcomes. You're starting to see new medications come up, increasing the number of medication options that are going to come out in the next few years and better tests and better ways and improving a knowledge how to prevent Alzheimer's disease and other dementias. I mean, the field is also making a lot of leaps in that. So, I think it's a very exciting time.

Glen Stevens, DO, PhD: Things that we haven't discussed that you think are important?

Jagan Pillai, MD, PhD: From our patient's perspective, the patients are counting on clinicians to make not just a diagnosis or just run a test. They are actually asking us to make this moment in their lives meaningful for them. So, they want a result, and it is a clinician who stands there and provides the information in the right context, in a way that's meaningful. And that may be a lot for each rushed clinician, but it's our duty to do due diligence and get educated so we are available for the patients in the best way possible.

Glen Stevens, DO, PhD: And I think we can't underscore what you just said there. And I think that is we do need to do the due diligence. We can all get lazy and just look at a blood test and go, "Oh, that's what you got." And just move on. But I think we have to remember who we are and what we do with patients, and it's just part of the whole that we're looking at with each individual patient.

Jagan Pillai, MD, PhD: Absolutely. You said it.

Glen Stevens, DO, PhD: So, I appreciate your joining me today. It's actually quite, even though maybe some of this sounds negative, it's quite exciting really that things are really moving forward. And I've never had a lumbar puncture, but I'd much rather have a blood test and a lumbar puncture if I could avoid it. So, these things are moving in the positive direction, maybe just going to move a little bit faster than we can keep up with exactly what we should tell patients. But I'm excited for you in the field.

Jagan Pillai, MD, PhD: Can I have a last word, Glen?

Glen Stevens, DO, PhD: Yes.

Jagan Pillai, MD, PhD: I would have to give a shout out for lumbar punctures because we have also research cohorts here where we study what's going on in the brain. And once a person gets in and get their lumbar puncture and cross a threshold, they are game for getting a second or the third, and then some of them inhabit every year. So, there you go. You just have to get that first one.

Glen Stevens, DO, PhD: Well, I'm still going to try and avoid that if I can personally, but I guess if I need one, I'll do it. Appreciate everything that you're doing and we'll give a positive shout out for the lumbar puncture. In the brain tumor field, we do a lot of lumbar punctures on patients as well. Appreciate what you're doing and look forward to seeing you in the future.

Jagan Pillai, MD, PhD: Thank you, Glen, for having me.

Closing: This concludes this episode of Neuro Pathways. You can find additional podcast episodes on our website, clevelandclinic.org/neuropodcast, or subscribe to the podcast on iTunes, Google Play, Spotify, or wherever you get your podcasts. And don't forget, you can access real-time updates from experts in Cleveland Clinic's Neurological Institute on our Consult QD website. That's @CleClinicMD, all one word. And thank you for listening.