New Study Finds Blood Test Can Predict Alzheimer’s Disease Progression Years Before Symptoms or Brain Scan Changes

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

A new study by investigators at Mass General Brigham has found that a blood test of plasma phosphorylated tau 217 (pTau217), an Alzheimer's disease biomarker, can predict the progression of amyloid PET scan changes and cognitive decline in cognitively healthy older adults. The findings may help push back the clock to enable simpler, earlier disease prediction and indicate who may be at risk for cognitive decline. The results are published in Nature Communications.

“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.”

Last year, the U.S. Food and Drug Administration cleared the first blood test for Alzheimer's disease, paving the way for a cheaper, less invasive alternative to lumbar punctures and PET scans. The new study by Yang and colleagues adds important evidence about the predictive potential of these kinds of blood tests. 

This prospective cohort study followed 317 cognitively healthy older adults from the Harvard Aging Brain Study (HABS) for an average of eight years. Participants, who ranged in age from 50 to 90 years, had blood tests for pTau217, repeated amyloid and tau PET scans and long-term cognitive testing. The researchers examined whether baseline and changing pTau217 levels predicted future amyloid buildup, tau accumulation (the abnormal buildup of misfolded tau proteins inside brain neurons) and cognitive decline.

Researchers found that higher levels of pTau217 predicted a faster buildup of Alzheimer's disease pathology, even when initial brain scans appeared normal. Increases in pTau217 frequently occurred before amyloid PET scans became positive, highlighting the biomarker's ability to detect changes earlier. Importantly, participants with low pTau217 levels at the start of the study were very unlikely to accumulate significant amyloid-beta on their PET scans over many years of follow-up.

“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.”

While it’s too early to recommend pTau217 testing for older adults, Yang and his colleagues hope the study results will serve as a scalable screening tool for clinical trials targeting Alzheimer's disease prevention and will help identify individuals at higher risk. Eventually, biomarker blood tests could be used for routine health maintenance and may offer a more affordable alternative to amyloid PET scans.

“As the field is evolving quickly, we’re excited to see discoveries on the research side being rapidly translated to clinical application,” said co-senior author Jasmeer Chhatwal, MD, PhD, a neurologist with Mass General Brigham Neuroscience Institute. “By anticipating who's going to turn amyloid-positive in the future, we are trying to push back the clock to enable earlier Alzheimer's disease prediction.”

Authorship: In addition to Yang and Chhatwal, Mass General Brigham authors include Juliana A. U. Anzai, Wai-Ying Wendy Yau, Brian C. Healy, Andrea M. Roman 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, Gad A. Marshall, Rebecca E. Amariglio, Dorene M. Rentz, Lei Liu, Dennis J. Selkoe, Keith A. Johnson, and Reisa A. Sperling. Additional authors include Philip B. Verghese and Joel B. Braunstein.

Disclosures: Philip B. Verghese and Joel B. Braunstein are full-time employees of C2N Diagnostics LLC. Other authors declare no directly relevant conflict of interest.

Funding: This work was supported by grants K23 AG062750, K23 AG084868, P01 AG036694 (Harvard Aging Brain Study), and R01 AG071865 from the National Institute on Aging, as well as the Shelby Cullom Davis Charitable Fund’s philanthropic gift.

Paper cited: Yang HS et al. “Plasma phosphorylated tau 217 and longitudinal trajectories of Aβ, tau, and cognition in cognitively unimpaired older adults” Nature Communications DOI: 10.1038/s41467-026-71269-3