A large international study suggests that very high p-tau217 levels may identify cognitively healthy adults who face a substantially greater chance of impairment years later.
A person can appear cognitively healthy while carrying biological changes linked to a greater chance of future cognitive decline. An international study led by researchers at the Mass General Brigham Neuroscience Institute has now estimated how strongly one blood marker, phosphorylated tau 217 (p-tau217), is associated with that risk over time.
The p-tau217 blood test recently received federal clearance, but its ability to forecast cognitive impairment in people without symptoms has remained uncertain. Researchers found that cognitively unimpaired adults with very high levels of the marker had a 38% absolute risk of developing cognitive impairment within five years.
The estimated risk was higher over the following decade. The findings were presented at the Alzheimer’s Association International Conference and published simultaneously in JAMA.
“We do not yet have disease-modifying treatments for people who find out they are at high risk for developing cognitive impairment due to Alzheimer’s disease, which is why we don’t recommend currently available blood tests for asymptomatic individuals. Today, our medical advice would remain the same regardless of test results: exercise regularly, maintain a healthy diet, and prioritize sleep and overall wellness,” said senior and corresponding author Reisa Sperling, MD, a neurologist with the Mass General Brigham Neuroscience Institute. “But the preventive care landscape could change rapidly if ongoing trials of disease-modifying therapies prove beneficial. In the future, these tests could help identify those who might benefit most from these treatments. Our long-term goal is to get us to where cholesterol testing is in predicting your risk of a heart attack.”
Six cohorts sharpened individual risk estimates
The researchers combined information from six observational studies and clinical trials conducted in North America, Japan and Australia. Together, the studies included 2,684 older adults who showed no cognitive impairment when they entered the research.
At enrollment, participants provided blood samples for p-tau217 testing and underwent PET imaging to establish baseline measurements. Their cognitive abilities were then evaluated during annual follow-ups. Enrollment in the earliest study began in 2004, while the latest follow-up included in the analysis took place in 2025.
By tracing changes in cognitive performance, the researchers calculated how the likelihood of impairment shifted over time. About 478 participants eventually developed cognitive impairment, and higher p-tau217 levels at the beginning of the studies were significantly associated with that progression.
Among people with very high concentrations of p-tau217, the estimated risk reached 38% within five years and 78% within 10 years. However, far fewer participants had been followed for a decade or longer, making those later estimates less certain than the five-year findings.
“This is a critical step toward better understanding what p-tau217 can tell us about a person’s risk for cognitive impairment,” said lead author Rachel F. Buckley, PhD, a cognitive neuroscientist with the Mass General Brigham Neuroscience Institute. “What really sets this work apart is that it estimates an individual’s level of risk for cognitive impairment. We harmonized data across six cohorts, creating a large and varied data set, and still found consistent results showing how p-tau217 informs risk over time.”
The signal held beyond known risks
The association between p-tau217 and later cognitive impairment remained significant even after researchers accounted for other established indicators. These included amyloid beta plaques visible on PET scans and genetic risk factors such as APOE4.
That suggests the blood marker may provide additional prognostic information rather than merely reflecting risks already captured by imaging or genetic testing. It could eventually help physicians estimate an individual’s likelihood of cognitive impairment more precisely.
Important limitations remain. The participant groups were affected by selection bias and may not represent the wider population. The analysis also focused primarily on risk over several years rather than across a person’s entire lifetime. Larger studies involving more representative populations and longer follow-up periods will be needed to confirm and refine the estimates.
For now, the researchers do not recommend routine p-tau217 testing for cognitively healthy people. Its clearest current use is identifying participants who face an elevated risk and may be suitable for Alzheimer’s prevention trials.
“Today, p-tau217 can help identify people at high risk for future Alzheimer’s dementia for participation in prevention trials,” said Sperling. “As these trials move forward, individualized estimates, including the biomarker’s prognostic value, could guide earlier treatment and monitoring decisions.”
Reference: “Prognostic Value of Blood-Based P-Tau217 Levels for Progression to Cognitive Impairment” by Rachel F. Buckley, Diana L. Townsend, Colin J. Birkenbihl, Madison Cuppels, Gillian T. Coughlan, Mabel T. Seto, Jane A. Brown, Michael J. Properzi, Merle C. Hoenig, Annie Li, Aaron P. Schultz, Jasmeer Chhatwal, Hyun-Sik Yang, Steven Arnold, Pia Kivisäkk, Bryan D. James, Sid O’Bryant, Robert A. Rissman, Melissa Petersen, Jessica Z. K. Caldwell, Tobey Betthauser, Julie Elisabeth Oomens, Maria Carrigan, Brian Healy, Jorge Garcia Condado, Sterling C. Johnson, Wai-Ying Wendy Yau, Oliver Langford, Michelle Farrell, Rebecca E. Amariglio, Dorene M. Rentz, Kathryn V. Papp, Ron Brookmeyer, Timothy J. Hohman, Michael Donohue, Paul S. Aisen, Keith A. Johnson and Reisa A. Sperling, July 14, 2026, JAMA.
DOI: 10.1001/jama.2026.12556
Funding: This study was funded in part by the National Institutes of Health (R01AG079142, DP2AG082342, U01 AG024904, R01AG054073, R01AG058533, R01AG070862, P41EB015922, U19AG078109, R01AG027161, R01AG021155, P30AG062715, U19AG010483, R01AG063689, P01 AG036694, P41EB015896, S10RR021110, S10RR023401, S10RR023043, P30AG062421), the U.S. Department of Defense (W81XWH-12-2-0012), Eli Lilly, the Alzheimer’s Association, Accelerating Medicines Partnership, the GHR Foundation, an anonymous foundation, private donors, and in-kind support from Avid, Cogstate, Albert Einstein College of Medicine, Foundation for Neurologic Diseases, and Meso Scale Diagnostics.
Disclosure: Buckley reported receiving grants from the National Institutes of Health (NIH) outside the submitted work. Sperling reported receiving grants from NIH (A4; R01 AG063689, U24AG057437), GHR Foundation, and Alzheimer’s Association during the conduct of the study; consulting for AbbVie, AC Immune, Acumen, Alector, Apellis, Biohaven, Bristol Myers Squibb, Ionis, Immunobrain, Janssen, Novo Nordisk, Oligomerix, Prothena, Roche, Therini, and Vaxxinity; and public-private partnership clinical trial funding from Eisai and Eli Lilly outside the submitted work. Additional author disclosures can be found in the JAMA paper’s disclosures section.
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