Announcements

Updates on campus events, policies, construction and more.

close  

Information for Our Community

Whether you are part of our community or are interested in joining us, we welcome you to Washington University School of Medicine.

close  


Visit the News Hub

Alzheimer’s protein in blood indicates early brain changes

Promising target for blood-based diagnostic test

by Tamara BhandariJuly 28, 2020

Matt Miller

Two decades or more before symptoms arise, plaques of a sticky protein called amyloid begin forming in the brains of people later diagnosed with Alzheimer’s disease. Researchers at Washington University School of Medicine in St. Louis have shown that levels of a specific protein in the blood rise as amyloid plaques form in the brain. This protein can be detected in the blood of people who have yet to show signs of forgetfulness or confusion, making it a promising blood test to diagnose Alzheimer’s before symptoms appear.

The findings are published July 28 in the Journal of Experimental Medicine.

“The finding of a unique tau species that is closely linked to changes caused by amyloid plaques will help to identify and predict people who have or will likely develop Alzheimer’s disease,” said senior author Randall J. Bateman, MD, the Charles F. and Joanne Knight Distinguished Professor of Neurology. “This will greatly accelerate research studies, including finding new treatments, as well as improving diagnosis in the clinic with a simple blood test.”

Alzheimer’s disease begins with a silent phase lasting two decades or more during which amyloid plaques slowly collect in the brain without causing obvious cognitive problems. For decades, researchers have been searching for an easy and affordable way to identify people in the so-called preclinical stage so that, once effective drugs are available, they could be treated and, ideally, never develop symptoms at all.

Positron emission tomography (PET) brain scans can identify people with amyloid plaques, but they are too time-consuming and expensive to be widely used for screening or diagnosis. Bateman and colleagues already are working on a blood test for amyloid that has shown promise at distinguishing people with amyloid in their brains from those without. But first author Nicolas Barthélemy, PhD, an instructor in neurology, Bateman and others realized that a different Alzheimer’s protein – tau – also may be useful for identifying which people have amyloid plaques silently gathering in their brains.

Barthélemy and Bateman previously had discovered that people with amyloid plaques tend to have certain forms of tau in the cerebrospinal fluid that surrounds their brains and spinal cords. Sampling the cerebrospinal fluid requires a spinal tap, which some participants are reluctant to undergo, but proteins in the cerebrospinal fluid can spill over into the blood, which is easier to obtain. If these specific forms of tau could be found in a person’s blood, they reasoned, that might be an indication that the person has the consequences of amyloid plaques in his or her brain.

To evaluate this possibility, the researchers analyzed blood samples and brain scans from 34 people participating in Alzheimer’s research studies at the university’s Charles F. and Joanne Knight Alzheimer’s Disease Research Center. Nineteen of the participants had no amyloid in their brains, five had amyloid but no cognitive symptoms, and 10 had amyloid and cognitive symptoms. The researchers used a technique known as mass spectrometry to identify and measure the different forms of tau in the blood samples. They found that levels of a form of tau known as phosphorylated tau 217 correlated with the presence of amyloid plaques in the brain. 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.

To verify their findings, the researchers repeated the analysis in a separate group of 92 people: 42 with no amyloid, 20 with amyloid but no cognitive symptoms, and 30 with amyloid and symptoms. In this analysis, levels of phosphorylated tau 217 in the blood correlated with the presence of amyloid in the brain with more than 90% accuracy. When the researchers looked only at people with no cognitive symptoms, blood levels of phosphorylated tau 217 distinguished those in the early, asymptomatic stage of Alzheimer’s disease from healthy people with 86% accuracy.

“This is just an exploratory study, but we think phosphorylated tau 217 is a promising target for an early diagnostic test,” Barthélemy said. “There was a large difference between the amyloid-positive and amyloid-negative groups, even amongst people who were cognitively normal. We did have to use a large volume of blood in this study, but we’re working on reducing the volume. Once we improve the way we are preparing and concentrating the sample, we will be a step closer to developing a tau-based blood test that can identify people at risk of developing Alzheimer’s dementia before symptoms arise.”

Barthélemy NR, Kanta K, Sato C, Bateman RJ. Blood plasma phosphorylated-tau isoforms track CNS change in Alzheimer’s disease. Journal of Experimental Medicine. July 28, 2020. DOI: 10.1084/jem.20200861

This study was supported by the Alzheimer’s Association; the Rainwater Charitable Foundation; the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (NIH), grant number R01NS095773; the Tau SILK Consortium (AbbVie, Biogen and Eli Lilly); and the Coins for Alzheimer’s Research Trust.

Washington University School of Medicine’s 1,500 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is a leader in medical research, teaching and patient care, ranking among the top 10 medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

Tamara covers infectious diseases, molecular microbiology, neurology, neuroscience, surgery, the Institute for Informatics, the Division of Physician-Scientists and the MSTP program. She holds a double bachelor's degree in molecular biophysics & biochemistry and in sociology from Yale University, a master's in public health from the University of California, Berkeley, and a PhD in biomedical science from the University of California, San Diego. She joined WashU Medicine Marketing & Communications in 2016. She has received three Robert G. Fenley writing awards from the American Association of Medical Colleges: a bronze in 2020 for "Mind’s quality control center found in long-ignored brain area," a silver in 2022 for "Mice with hallucination-like behaviors reveal insight into psychotic illness," and a bronze in 2023 for "Race of people given Alzheimer’s blood tests may affect interpretation of results." Since January of 2024, Tamara has been writing under the name Tamara Schneider.