By Brandon Chase
Mass General Brigham Hospital
April 25, 2026

Mass General Brigham researchers used long-term data and a blood test for the biomarker pTau217 to identify the earliest signs of Alzheimer’s disease in cognitively healthy adults.

A team of investigators at Mass General Brigham reports that a blood test measuring plasma phosphorylated tau 217 (pTau217), a biomarker linked to Alzheimer’s disease, can forecast changes seen on amyloid PET scans as well as later cognitive decline in older adults who currently show no signs of impairment.

These findings suggest it may be possible to identify risk much earlier and with simpler tools, opening the door to earlier intervention. The study appears in Nature Communications.
Blood marker signals disease earlier

“We used to think that 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 and an associate member of the Broad Institute of MIT and Harvard. “But now we are seeing that pTau217 can be detected years earlier, well before clear abnormalities appear on amyloid PET scans.”

The U.S. Food and Drug Administration approved the first blood test for Alzheimer’s disease last year, marking an important shift toward more accessible and less invasive diagnostic options compared with lumbar punctures and PET imaging. Building on that progress, Yang and colleagues provide further support that blood-based biomarkers can serve as early indicators of disease processes that were previously detectable only through imaging.
Long-term study tracks early changes

In this prospective cohort study, researchers tracked 317 cognitively healthy adults enrolled in the Harvard Aging Brain Study (HABS) for roughly eight years. Participants, aged 50 to 90, underwent repeated blood testing for pTau217 alongside amyloid and tau PET scans and detailed cognitive assessments. The team analyzed whether both initial levels and changes in pTau217 could anticipate future amyloid buildup, tau accumulation (the abnormal buildup of misfolded tau proteins inside brain neurons), and declines in cognitive performance.

The results showed a clear pattern. Individuals with higher pTau217 levels experienced more rapid development of Alzheimer ‘s-related changes, even when their early brain scans appeared normal. In many cases, increases in the biomarker were observed before amyloid PET scans showed positive results, underscoring its sensitivity to early disease activity. By contrast, participants who began the study with low pTau217 levels were unlikely to show meaningful amyloid accumulation over the years that followed.

“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.”
Toward earlier Alzheimer’s detection

Although pTau217 testing is not yet ready for routine clinical use, the colleagues see potential for it to play a key role in screening participants for prevention trials and identifying those at elevated risk before symptoms emerge. With further validation, such blood tests could become part of regular health monitoring and provide a lower-cost alternative to imaging-based methods.

https://www.nature.com/articles/s41467-026-71269-3

Reference: “Plasma phosphorylated tau 217 and longitudinal trajectories of Aβ, tau, and cognition in cognitively unimpaired older adults” by Juliana A. U. Anzai, Brian C. Healy, Andrea M. Román Viera, Courtney Maa, Dylan Kirn, Michael J. Properzi, Jean-Pierre Bellier, Aaron P. Schultz, Michelle E. Farrell, Heidi I. L. Jacobs, Rachel F. Buckley, Kathryn V. Papp, A. Marshall, Rebecca E. Amariglio, Dorene M. Rentz, Hyun-Sik Yang, Dennis J. Selkoe, Philip B. Verghese, Joel B. Braunstein, Keith A. Johnson, Reisa A. Sperling