Ongoing Research and Use of Biomarkers and Imaging in Alzheimer’s Disease

EP: 1.Current Understanding of Alzheimer’s Disease Pathology

EP: 2.Biomarkers and Challenges to the Use of Biomarkers in Alzheimer’s Disease

EP: 3.Genetic and Structural Heterogeneity in Alzheimer’s Disease

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EP: 4.Ongoing Research and Use of Biomarkers and Imaging in Alzheimer’s Disease

EP: 5.Diagnostic Pathway for Alzheimer’s Disease

EP: 6.Importance of Primary Care Physicians in Diagnosis of Alzheimer’s Disease

EP: 7.Use of ATN Classification for Alzheimer’s Disease in Clinical Practices

EP: 8.Factors Contributing to Clinical Trial Failures in Alzheimer’s Disease

EP: 9.Considerations for Management of Alzheimer’s Disease

EP: 10.Current Treatment Options for Alzheimer’s Disease

EP: 11.Management of Neuropsychiatric symptoms of Alzheimer’s Disease

EP: 12.Treatment Pipeline for Alzheimer’s Disease

EP: 13.Aducanumab for Treatment of Alzheimer’s Disease

EP: 14.Management of Amyloid Related Imaging Abnormalities (ARIA) for Alzheimer’s Disease

EP: 15.Lecanemab for Treatment of Alzheimer’s Disease

EP: 16.Other Anti-Amyloid Antibody Agents for Treatment of Alzheimer’s Disease

EP: 17.Data from Other Emerging Alzheimer’s Disease Treatment Options from CTAD 2022

EP: 18.Prevention Trials in Alzheimer’s Disease

EP: 19.Future Outlook for Alzheimer’s Disease

Marwan Sabbagh, MD: We started to discuss biomarkers, Dr Atri. Because we all agree that the emergence of the CS7 plasma biomarkers is starting to get some traction. Would you comment please on the updates on plasm biomarkers that you’ve seen here at CTAD 2022 or in other meetings and also talk about CSF [cerebrospinal fluid] or plasma? And what else are you excited about?

Alireza Atri, MD, PhD: Yes. Again, we’re in an exciting era for biomarkers. Some need more validation than others. Going back to CSF, I’m still an advocate CSF. Not everybody can have CSF. But the nice thing about CSF is it’s quantitative.

Marwan Sabbagh, MD: Yes.

Alireza Atri, MD, PhD:And it gives you information about a number of different types of biomarkers. It can give you information about the amyloids, a-beta 42, 40, pTau, total tau, NfL, neurogranin, a whole bunch of different things in a sequestered area, in a protected area that’s different from the plasma where the levels are orders of magnitude different, and not affected by all the things that are in the blood: medicines, proteins, other things. But not everybody can get it, and there’s kind of a misconception about potentially how painful it is or how difficult a procedure it is. I like CSF; it’s available. It’s scalable. We need to do a better job of that in the United States. What it can’t tell you is…the information like a PET scan does, of location. It’s quantitative in one way, but it can’t tell you the information. With PET scans, obviously with amyloid, you can read it in different ways. In a clinical way, usually it’s yes/no, binary. Few things in life are binary. But this is something that has an intermediate zone, and we still have to understand a bit about regional differences, etcetera. There’s cost and radioactivity involved with PET scans. With tangles and tau, that’s also available, and it seems like—Dr McDade was mentioning this—symptoms tend to go along a bit more with tangle deposition. That’s going to be useful for us to understand and look at. With the blood biomarkers that I’m excited about, that we’ve seen a lot of data about, is what can we do early on to potentially maybe, in some people, we need very accurate diagnosis, and later on maybe treatments we can follow with blood. There are different parts for pTau, there are different type of epitopes you can measure: 181, 217, 231. The consensus, maybe you can tell me what you’ve seen, is that 217 seems to be good with looking at progression. It’s good and it correlates well with amyloid plaques. But early on in a population, this may be not clinical yet. Maybe 231 sounds like it has a lot of promise. We have to think, a biomarker of what? Is it biomarker of risk or trait? That’s a good one, is ApoE4. That’s a big, that and age together. We’re thinking of single biomarkers, but ultimately with blood, we’re probably going to have multiple. We’re going to have to put things together. Then we can think about biomarker of states, so you’ve got the disease, maybe 231 early, 217 later on. Biomarker of progression or response, pTau 217 will be a good one. Ultimately, the final common pathway for causing symptoms is going to be neuronal damage and synaptic damage. We need to understand a bit more about that. Neurogranin, we’ve seen a bit of data here that seems to be promising, but we’re probably years away from a clinical standpoint to use that. NfL has been used for a while, but again, we’re a bit uncertain about the mechanisms about maybe removing amyloid and having effect on that, and how that may ultimately affect these biomarkers. One of the other things is that if you have treatments, what are, for how long, and how much, as Dr McDade was saying, for different individuals do you have to suppress amyloid, lower amyloid? Are there going to be temporal lags? And what are the other types of mechanisms, resilience and vulnerability, that are going to make people have better responses? In some ways we have Alzheimer’s diseases for different people, going back to your genetic heterogeneity that we need to understand better. It’s going to probably take us another 10 to 15 years easily, to get personalized medicine. But the biomarkers are being developed.

Transcript edited for clarity