Blood-Based Biomarkers in Alzheimer Disease

Alireza Atri, MD, PhD: Continuing to look ahead, there has recently been talk about biomarkers from the blood. What are the prospects for that, Brad?

Bradford C. Dickerson, MD: Well, I think we’ve seen the field truly revolutionize with biomarkers of amyloid and tau in the spinal fluid or measured through PET [positron emission tomography] scans. I think the holy grail is that there would be at least a sensitive, if not specific, blood test that could help us triage the patients for whom we spend a lot of money getting PET scans on or ask to do an invasive procedure like a spinal fluid examination on.

We’ve seen more reports recently of progress on very sensitive assays to detecting both forms of amyloid and forms of tau in the blood. And so I think most biologists who are working in this area, and neurologists that are also neuroscientists doing this work, are optimistic that it won’t be too long before we have a blood test. It may not be the final answer, but it will help us decide whether we need to move forward with more expensive, more invasive tests that we have available now.

I hope that it won’t just be that. I think we’ll be seeing some progress in genetic factors that can be measured increasingly easily from blood, that would allow us to identify the so-called polygenic risk scores that enable us to look at the multigenetic loading that people may have, that either make them more likely to develop Alzheimer disease or more likely to develop 1 of the other forms of neurodegenerative disease. And again, that’s probably a risk stratification type of test that will, I think, be available at some point in the future. Those are some of the things in the blood.

I think we’ll see new spinal fluid biomarkers that enable us to measure the neurodegenerative progression of these diseases and, potentially, have other markers for readouts in clinical trials. And maybe they’ll even prognosticate better with regard to these other processes, like neuro-inflammation, that are potentially exacerbating the condition. And of course, new PET [positron emission tomography] scans that will enable us to measure frontotemporal lobar degeneration pathology markers or Lewy body pathology markers.

The other thing that doesn’t get talked about as much, in terms of the future of biomarkers, is measures of circuit function and dysfunction. We often think about FDG-PET [fluorodeoxyglucose-PET] or functional MRI [magnetic resonance imaging], but there’s an increasing effort to develop more accessible tools with electrophysiology, in particular, that might allow us to measure, in a more accessible way, the functioning of brain systems—in a way that’s more sophisticated than conventional EEG [electroencephalography], used clinically. And I think that will potentially relate to some of the efforts to develop treatments targeting circuits that may be what you would consider to be neuromodulation or neurostimulation technologies that I think are coming along as exciting, as we’ve seen them become efficacious in the field of major depressive disorder. I think we’re hoping that they might actually be tools that would become part of our treatment strategies in the future for some of these neurodegenerative diseases, especially in the early stages.

Alireza Atri, MD, PhD: I’m very excited too. I think in the next 2, 3, 5 years, we’re going to have blood tests that are going to really help us detect some of these things and get people the attention that they need; including going into studies and clinical trials. Actually, I want to ask you, Marc, if people want to turn to clinical trials—if they want to learn about them—where should they go?

Marc E. Agronin, MD: We need more people participating in clinical trials. That’s the bottom line. Obviously, Clinicaltrials.gov is a good clearinghouse. But I think for the average caregiver or patient, that can be overwhelming. The Alzheimer’s Association has a TrialMatch entity that is very helpful, and that’s a good way to get started. And there are always advertisements locally that people can find because there are so many trials going on.

But I think going through an organization such as the Alzheimer’s Association is sometimes the best, because anything registered with that is going to be a well-vetted trial. People need to know that there should never be a cost to be part of a trial. They need to understand the role of placebos and that they have full rights throughout a trial. That education is key to get more people involved in those different, really critically important trials.

Transcript edited for clarity.