COMMENTARY

Is Tau Blood Testing a Game Changer for Diagnosing Alzheimer's?

Adam L. Boxer, MD, PhD; Rudolph E. Tanzi, PhD; Samuel E. Gandy, MD, PhD

Disclosures

September 29, 2020

This transcript has been edited for clarity.

Adam L. Boxer, MD, PhD: This recent study led by Oskar Hansson in Sweden used a new blood test that measures the levels of a protein called phosphorylated tau 217 (P-tau217) in plasma.

Samuel E. Gandy, MD, PhD: The authors show comparable sensitivity to the most standard ways of confirming a diagnosis of Alzheimer's disease (AD) now, which are positron emission tomography scan and lumbar puncture and spinal fluid exam.

Boxer: The group looked at the results in three different patient cohorts, including one that had their brains analyzed upon autopsy by neuropathologists. Therefore, it could be shown that they had the gold-standard diagnosis, which we call definite AD.

Gandy: They also looked at a Colombian family where there was a mutation in the PSEN1 gene that causes early-onset familial AD. That actually gave them a leg up on identifying this new particular phosphorylated form of tau, which is part of what provides this breakthrough. This is testing for a particular phosphorylation site that has not been widely associated with tau until now.

Rudolph E. Tanzi, PhD: This is a typical AD cohort in terms of age and distribution of sex. What they found was that P-tau217 did differentiate AD from non-AD with much higher accuracy than plasma phosphorylated tau 181 and even better than neurofilament light chain, which is actually quite good. And it was even better in cohort 2 (Swedish BioFINDER-2). In cohort 3, which comprised Colombian autosomal-dominant AD kindreds, they found that P-tau217 levels were even greater among the PSEN1 mutation carriers for early-onset AD compared with noncarriers. Quite extraordinarily, they started seeing P-tau217 approximately 20 years before symptoms.

Gandy: The test determines the presence of AD pathology. We know from decades of work that the pathology doesn't perfectly match the clinical picture. For example, about 25% of patients at presentation have clinical AD but don't yet have amyloidosis. So those folks would give a potential confounding reading on this blood test.

Boxer: And it's not yet clear how the test will perform in the community in people who may have other comorbidities or may be taking other drugs. Then there is the need to look at other potential confounding factors, such as other illnesses, medications, and different age groups that might potentially affect the accuracy.

Tanzi: We do need to see optimization of this assay for commercial use, and the findings still need to be validated in more diverse populations. Here they used very select cohorts. I think we now need to see a larger trial in diverse populations that are not biased, for example, toward a certain mutation like PSEN1.

Gandy: I think the potential impact of the study is to increase the confidence of the diagnosis of AD in the population at large and perhaps elevate the level of the conversation so that people appreciate just how common AD is.

Boxer: When we look at the results of this study, along with work that's been done in our group at University of California, San Francisco, using the same blood test and a study led by Randall Bateman's group at Washington University, what's really remarkable is that the results are nearly identical in three different independent laboratories and multiple different independent groups of people.

Tanzi: This test is probably the best I've yet seen for something that could be turned into an early detection and intervention strategy for reducing risk for or even preventing AD.

Boxer: I strongly believe that this blood test is going to be a game changer for our clinical practice — taking care of older people with cognitive impairment and dementia — but also particularly in the development of new therapies.

Dr Boxer is director of the Neurosciences Clinical Research Unit and Alzheimer's Disease and Frontotemporal Degeneration Clinical Trials Program at the UCSF Memory and Aging Center in San Francisco, California.

Dr Tanzi is the Joseph P. and Rose F. Kennedy Professor in the Harvard Medical School Department of Neurology, and also vice chair of neurology research and director of Genetics and Aging Research United at Massachusetts General Hospital in Boston, Massachusetts.

Sam Gandy, MD, PhD, is director of the Mount Sinai Center for Cognitive Health at Mount Sinai Hospital in New York City.

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