One Barrier to Alzheimer’s Diagnoses Could Crumble With Discovery of a Blood Biomarker

PITTSBURGH (Pittsburgh Post-Gazette/TNS/Hamodia) — Researchers at University of Pittsburg say that they’ve discovered a blood marker which can potentially help in diagnosing Alzheimer’s disease. Alzheimer’s, a progressively debilitating condition which causes memory loss and other cognitive problems, affects 6.7 million Americans.
Alzheimer’s is a costly disease to manage as well; the Alzheimer’s Association expects the U.S. to spend $345 billion on it in 2023.

Published in Nature Medicine on Monday, a study found a new biomarker, or “tag,” for Alzheimer’s by looking at the blood samples of 1,016 participants.

“When you look at all the biological definitions of Alzheimer’s, it says it’s a condition of amyloid and tau,” said senior study author, Dr. Tharik Pascoal, associate professor of psychiatry and neurology at Pitt. “This study provides an update,” he said, and addresses a “key piece of the puzzle” in understanding how Alzheimer’s progresses.

The study is a collaboration between scientists at Pitt’s Psychiatry department, the University of Gothenburg in Sweden, McGill University in Canada and the biotech company Janssen. It was partially funded by the Alzheimer’s Association, National Institute on Aging, and National Heart Lung and Blood Institute.

Scientists have long known that people with Alzheimer’s develop a build-up of proteins called amyloid-beta, which coat neurons and slow them down. Another protein called tau gets tangled inside neurons, further adding to Alzheimer’s pathology.

But in the present study, research might have discovered a main reason why some people with brains full of amyloid plaques never experience profound cognitive impairment, while others do. The answer lies in a kind of brain cell that has been largely underappreciated by scientists for decades: astrocytes.

Astrocytes are helper cells in the brain that respond to injury and facilitate communication among neurons, vital for metabolism and clearing waste. But because they don’t conduct electricity like neurons do, many scientists had cast them aside in the early days of academic research.

The scientists found that the blood samples of some participants revealed an important biomarker: GFAP. This protein is released by astrocytes in response to injury and can be thought of as a signal for how reactive astrocytes are in the brain.

Many of the participants’ blood showed signals of amyloid and tau, but only some had the GFAP biomarker for astrocyte reactivity. The scientists watched three cohorts of participants over a span of years and discovered that those with GFAP would go on to show signs of Alzheimer’s symptoms, while those with only amyloid or tau would not. And these results were consistent across three cohorts, despite them consisting of different participants over different years.

“This puts astrocytes at the center as key regulators of disease progression, challenging the notion that amyloid is enough to trigger Alzheimer’s disease,” said Dr. Pascoal in a news release about the study. Not only does this change the way researchers can envision Alzheimer’s progression, but it also introduces an important consideration for early detection of the disease. The GFAP biomarker test could be added to blood panels and given during a simple doctor visit, increasing access to early Alzheimer’s diagnosis.

Dr. Pascoal said all UPMC physicians are expected to have an opportunity to add this blood test to their gamut.

“This means it can be useful very fast. I think it’s coming very soon,” he said.

Emily Largent, an assistant professor of medical ethics and health policy at the University of Pennsylvania Perelman School of Medicine, and specializing in Alzheimer’s drug regulation, said replicating these findings will be important to confirm how the scientific community can understand and move forward with the results.

“Hopefully, blood-based tests will lower two long-standing barriers to the uptake of Alzheimer’s biomarker testing: high cost and high patient burden. Blood-based tests are relatively cheaper and less burdensome to undergo than the alternative imaging tests,” she said in an email. Largent was not involved in the research.

“Lowering barriers and increasing access to biomarker testing is increasingly important as drugs that can slow the progression of cognitive impairment are made available to patients living with cognitive impairment caused by Alzheimer’s disease.”

There are many risk factors for Alzheimer’s disease, some imprinted and others changeable. Genetics and family history play a part in who develops the disease because it can be passed down through our DNA. Other immutable factors, such as age, race and gender play a role as well: Women are more likely to develop the disease, as are black Americans, who are twice as likely as whites to have Alzheimer’s.

Larkins-Pettigrew thinks this is due in part to chronic stress from structural problems, such as food insecurity, poverty, lack of education and lack of access to quality health care. Chronic stress impacts heart health and inflammation, and can accelerate aging.