New Blood Biomarker Tests for Alzheimer’s Called a Game Changer

Researchers have identified a blood-based biomarker called P-tau217 that distinguishes Alzheimer’s from other neurodegenerative disorders.

Everyday Health Archive
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Years of research have gone into finding a reliable blood biomarker for Alzheimer’s disease.Anastasia Usenko/iStock

A simple blood test for Alzheimer’s disease — one that could transform the way this degenerative and deadly disease is diagnosed — could be closer than ever to reality, according to research presented at the 2020 Alzheimer’s Association International Conference.

On Tuesday, scientists reported results of multiple studies on advances in blood tests for abnormal versions of the tau protein, an important driver of Alzheimer’s disease. In particular, the studies focused on a form of tau known as plasma phospho-tau217 (P-tau217) that appears to be the most specific to the disease.

“This is a game changer, because previously we relied on autopsy, brain imaging, or cerebrospinal fluid assays to see what is happening in the brain,” says Barbara Bendlin, PhD, an associate professor of medicine at the University of Wisconsin in Madison, who was not involved with the presented studies.

“Determining brain pathology using a blood-based biomarker would facilitate screening, could make testing more widely accessible, and may be easier or less costly than some other techniques for determining brain pathology,” says Dr. Bendlin.

A Pressing Need for an Accurate Diagnostic Test

According to the Alzheimer’s Association, 5.8 million Americans age 65 and older are living with Alzheimer’s disease. By 2050 the number is expected to rise to 14 million.

At present there is no single diagnostic test that can determine whether a person has Alzheimer’s disease. Physicians typically rely on medical history, mental status tests, and physical and neurological exams in forming a diagnosis. Brain imaging, including MRI or CT scans, are sometimes part of an evaluation, but they are more generally used to rule out other conditions.

This makes the prospect of a reliable blood test even more exciting for patients and clinicians alike.

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How P-tau217 Research Evolved

Researchers at Washington University School of Medicine in St. Louis previously found that P-tau217 accumulates in the cerebrospinal fluid of Alzheimer’s patients before the onset of cognitive symptoms, increases with disease progression, and can be used to accurately predict the formation of amyloid plaques. They suspected that P-tau217 might also be present in the blood of people with Alzheimer’s.

The scientists proceeded to develop a mass spectrometry–based method that could measure minute amounts of P-tau217 and other tau fragments in the blood. They found that people with amyloid in their brains had two to three times more of the protein in their blood than people without amyloid. These high levels were evident even in people with no signs of cognitive decline. The team also found that P-tau217 correlated more closely to amyloid buildup in the brain than another form, P-tau181, previously proposed as a biomarker for Alzheimer’s disease.

The results led the researchers to target P-tau217 for an early diagnostic test, and their findings were published on July 28, 2020, in the Journal of Experimental Medicine and presented that day at the 2020 Alzheimer’s Association International Conference (AAIC).

Commenting on the study, Paul Rosenberg, MD, a professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine in Baltimore, states, “The most remarkable thing is that P-tau predicted amyloid in the brain. It’s not just a matter of a better chemical test — this is biology. When the plasma tau was elevated, it was an excellent predictor of having amyloid in the brain.”

The senior author of the study, Randall J. Bateman, MD, the Charles F. and Joanne Knight Distinguished Professor of Neurology at Washington University School of Medicine in St. Louis, is similarly enthusiastic: “It’s transformational,” Dr. Bateman says, describing the tau-based blood test, which he says could be available within a year.

Bateman adds, “For developing better treatments, a blood test will allow for quicker enrollment, which means faster trials, which will lead us to highly effective treatments much faster.”

A Second Study Shows That P-tau217 Differentiates Alzheimer’s From Other Diseases

In a second study, presented at AAIC the same day and published on July 28, 2020, in the Journal of the American Medical Association, an international team of researchers reported on their cross-sectional study of 1,402 people to determine the usefulness of a blood biomarker test they developed to distinguish Alzheimer's from other diseases.

Their key finding: blood P-tau217 could distinguish Alzheimer’s from other neurodegenerative disorders with a diagnostic accuracy between 89 and 98 percent. The researchers estimate that their test could be available for clinical use in as little as two to three years.

Accurate Diagnostic Tests Could Speed Up Clinical Trials

Experts agree that blood tests for Alzheimer’s, which are being developed by several research teams, could greatly improve the screening process for clinical trials.

“Currently CSF (cerebrospinal fluid) or amyloid and tau PET scans are used to screen for clinical trials,” says Jonathan Graff-Radford, MD, a neurologist at the Mayo Clinic in Rochester, Minnesota. “But they are invasive or expensive. A blood test could be used to screen a large number of possible participants, and only the subset with a positive blood test would go on to get the more invasive or expensive CSF or PET scan. This would allow trials to enroll more rapidly and at a decreased cost,” says Dr. Graff-Radford.

In addition to improving the rigor of clinical trials, biomarkers such as the P-tau217 blood test may prove to be equally important in the clinical setting. These blood tests would allow doctors to diagnose or rule out Alzheimer’s in people with dementia. In addition, they could eventually be used earlier, allowing people who display early signs of memory loss to learn whether they will develop Alzheimer’s or instead have another condition.

Blood Test Details Still to Be Worked Out

While the prospects of blood tests are exciting, experts caution that there’s still work to be done.

“For example, it will be necessary to determine what is a normal result versus an abnormal result,” says Bendlin. “It could mean very different things to be positive for Alzheimer’s pathology in your fifties compared to in your eighties.”

“Levels of proteins in blood could perhaps point toward disease severity, which may determine who should be treated,” she adds.

And just like a brain scan, these blood tests will need to be interpreted in the context of other factors, says Aaron Ritter, MD, an associate staff member in neuropsychiatry and behavioral neurology at Cleveland Clinic's Lou Ruvo Center for Brain Health in Las Vegas. “We still don’t know whether these tests may be affected by other neurological disease processes like stroke, tumor, poor sleep, etc. So for me, it is still a wait-and-see.”

With Better Diagnostics, a Hope for Targeted Treatments

In addition to expediting clinical trials and making diagnoses more accurate and accessible, a reliable blood test for Alzheimer’s could usher in an era of targeted treatments, like those currently used for certain cancers and other diseases and conditions.

“The P-tau217 blood test is a breakthrough,” says Howard Fillit, MD, the founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation in New York City. “And I think there will be others that will follow, which will enable ‘precision medicine’ for Alzheimer’s disease, defining many subtypes based on the biomarker profile, with combination therapies also based on the biomarker profile.”