Alzheimer's Blood Test May Also Detect Advanced CTE, Study Finds

What do Alzheimer's disease and CTE have in common?

Both diseases involve clumps of a protein called tau, which normally helps support the internal structure of nerve cells. Tau comes in two main forms. In some tau diseases, only one form clumps; in Alzheimer's and CTE, both do.

Horie; co-senior author Chihiro Sato, PhD, an assistant professor of neurology; and co-author Randall J. Bateman, MD, the Charles F. and Joanne Knight Distinguished Professor of Neurology, previously showed that blood levels of eMTBR-tau243 track tau clumps in the brains of people with Alzheimer's. The team then asked whether the biomarker was specific to Alzheimer's or common to other tau-related diseases, known as tauopathies.

How did researchers discover the link to CTE?

Horie, Sato and collaborators at UC San Francisco made the connection while testing eMTBR-tau243 in samples from more than 80 people whose brain diseases were confirmed at autopsy, plus healthy volunteers. As expected, levels were very high in Alzheimer's and low in diseases where only one form of tau accumulates.

Then one patient stood out. The autopsy showed no signs of Alzheimer's, yet the biomarker level was unexpectedly high. Horie combed through the autopsy records and found advanced CTE in that person's brain.

The researchers went on to test blood from 11 people whose CTE was confirmed at autopsy. Their eMTBR-tau243 levels ran higher than in healthy people and rose with the severity of disease.

"Our study shows that an Alzheimer's disease biomarker can be applied to other tauopathies, including CTE," Sato said.

There are limits. The test distinguished advanced CTE from healthy controls with high accuracy but couldn't reliably catch early-stage disease. Levels in CTE were also much lower than in Alzheimer's.

The full study included 229 participants drawn from several biorepositories, including one at WashU Medicine. Researchers analyzed samples at the university's Tracy Family SILQ Center using a mass spectrometry assay — a technique that precisely measures molecules in blood.

Can patients get tested for CTE now?

Not yet. WashU has licensed the eMTBR-tau243 technology to C2N Diagnostics, a WashU startup that already developed an FDA-cleared blood test to aid Alzheimer's diagnosis. The test has not been validated for diagnosing CTE, and larger studies are needed before any clinical use for that purpose.

There's another catch: because the protein is also high in Alzheimer's — a disease that often occurs alongside CTE — the biomarker alone can't tell the two apart.

"This is not going to be a standalone biomarker," Sato said. "But if someone has a history of repeated head injury, tests negative for Alzheimer's, and this biomarker comes up, it might be CTE."

For Horie, the stakes extend beyond a single disease. "My dream is to clear tauopathies all over the world," he said. "This work broadens therapeutic opportunities beyond Alzheimer's disease."