Blood Biomarker Can Predict Signs of Alzheimer’s Before PET Scans

A blood test that measures plasma phosphorylated tau 217 is capable of predicting future Alzheimer’s disease onset in cognitively normal older adults even when positron emission tomography scans do not show amyloid or tau build up in the brain.

“We used to think that positron emission tomography (PET) scan detection was the earliest sign of Alzheimer’s disease progression, revealing amyloid accumulation in the brain 10 to 20 years before symptoms appear,” said lead author Hyun-Sik Yang, MD, a neurologist with Mass General Brigham Neuroscience Institute, in a press statement.

“But now we are seeing that phosphorylated tau 217 (pTau217) can be detected years earlier, well before clear abnormalities appear on amyloid PET scans.”

In 2025, the FDA approved two blood tests for Alzheimer’s disease, one that compares the ratio of pTau217 to beta amyloid developed by Fujirebio and a pTau181 plasma test developed by Roche. However, both of these tests are only indicated for people who already have some symptoms of the condition.

The current study, published in Nature Communications, aimed to test whether pTau217 in the blood can forecast beta‑amyloid and tau build‑up in the brain before individuals become amyloid‑positive on PET scans.

Overall, 317 older adults, aged 72 years on average, from the Harvard Aging Brain Study were included in the study. About 60% were women. There were no signs of cognitive decline on enrollment, and the group had a high education level. The researchers followed up 245 people in the group with repeat amyloid scans for about six years on average.

The test was able to pick up cases where beta amyloid was visible on brain scans with a high level of accuracy. The study also showed that higher starting pTau217 levels predicted faster amyloid build‑up over time, even after accounting for age, sex, and APOE status

Centiloid units are the standard scale for amyloid on brain scans with 100 centiloids typical of full-blown disease. The team found that the test could also predict future amyloid buildup even if no signs could be seen on initial PET scans. Each one‑percentage‑point increase in pTau217 at baseline was linked to an extra 0.35 centiloid units of amyloid buildup per year. Notably, those with low pTau217 levels on enrollment were still amyloid negative on scans years later.

“What stood out in our study is that even when amyloid scans appear normal in the clinic, the pTau217 biomarker can identify individuals who later become amyloid-positive,” said Yang. “It also shows that those with low pTau217 levels are likely to stay amyloid-negative for several years.”