A simple blood test could help identify people at increased risk of Alzheimer’s-related cognitive decline years before they experience noticeable problems with memory or thinking. In a large international study, researchers found that older adults with very high levels of a particular blood biomarker had a 38% chance of developing cognitive impairment within five years. Over 10 years, the estimated risk increased to 78%, although longer-term results are based on much less data.
The findings offer new insights into the potential of blood tests to predict future cognitive problems in people who currently show no signs of impairment. The research was led by scientists at the Mass General Brigham Neuroscience Institute and involved teams working on three continents. The results were presented at the Alzheimer’s Association International Conference and simultaneously published in JAMA.
The study focused on phosphorylated tau 217 (p-tau217), a blood biomarker associated with Alzheimer’s disease. A test measuring this marker recently received federal authorization, raising hopes that blood tests could make detection of Alzheimer’s disease more accessible. However, an important question remains: Can these tests reliably predict whether a person with normal cognitive function will eventually develop symptoms?
Blood test reveals risk of cognitive decline years in advance
To investigate, researchers combined information from six observational studies and clinical trials conducted in North America, Japan and Australia. Together, these studies included 2,684 older adults who had no signs of cognitive impairment at the time of their research participation.
During enrollment, participants provided blood samples that were analyzed for p-tau217. They also underwent positron emission tomography (PET) brain scans, allowing researchers to establish baseline measures of brain health. Annual follow-up assessments were then used to monitor changes in memory, thinking, and other cognitive abilities.
The combined data covered an unusually long period. Some participants took part in one of the studies as early as 2004, while the most recent follow-up assessments took place in 2025.
Across all studies, approximately 478 participants ultimately developed cognitive impairment. When the researchers compared these results with the results of the original blood tests, they discovered a strong relationship between higher levels of p-tau217 and the likelihood of future cognitive problems.
Among people with very high biomarker levels, the estimated probability of developing cognitive impairment reached 38% within five years. In 10 years, this figure rose to 78%. However, the researchers pointed out that far fewer observations were available for the 10-year period and beyond, making these longer-term predictions less certain.
A powerful predictor of Alzheimer’s disease beyond genetics and brain scans
One of the most important findings was that p-tau217 provided information about future cognitive decline beyond what could be explained by other established risk factors.
The biomarker remained significantly associated with cognitive impairment even after researchers took into account beta-amyloid plaques, which are abnormal protein deposits in the brain that can be detected by PET imaging. Its predictive value also extended beyond known genetic risk factors (such as APOE4).
This suggests that a relatively simple blood test could potentially provide doctors with additional information to estimate the likelihood that an individual will develop cognitive difficulties.
“This is a crucial 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 at the Mass General Brigham Neuroscience Institute. “What really sets this work apart is that it estimates an individual’s level of cognitive impairment risk. We harmonized data from six cohorts, creating a large and varied dataset, and yet found consistent results showing how p-tau217 informs risk over time.”
Rather than simply identifying biological changes associated with Alzheimer’s disease, research estimates how these changes translate into the likelihood of developing symptoms over a specific period of time.
Why blood tests for Alzheimer’s disease are not yet recommended for healthy people
Despite these promising results, the researchers caution that blood tests are currently not recommended for routine screening of Alzheimer’s risk in asymptomatic people.
One of the main reasons is that preventive treatments capable of modifying the course of the disease have not yet been developed for otherwise healthy individuals identified as being at high risk.
“We do not yet have disease-modifying treatments for people who discover they are at high risk of developing cognitive impairment from Alzheimer’s disease, so we do not recommend currently available blood tests for asymptomatic people. Today, our medical advice would remain the same regardless of test results: exercise regularly, maintain a healthy diet, and prioritize sleep and general well-being,” said lead and corresponding author Reisa Sperling, MD, neurologist at Mass General Brigham Neuroscience Institute. “But the landscape of preventive care could change quickly 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 tests are to predict your heart attack risk.”
There are also important limitations to the research. Although investigators gathered data from multiple studies and geographic regions, participants may not fully represent the population as a whole. This potential selection bias could affect how the results apply to other groups.
Additionally, the analysis focused on predicting cognitive impairment over relatively limited periods rather than estimating a person’s risk over their lifetime. The researchers say larger, more representative studies and longer follow-up periods will be needed to confirm the findings and improve the accuracy of individual risk predictions.
Could blood tests help prevent Alzheimer’s disease before symptoms appear?
The greatest potential benefit of this approach may come as scientists develop treatments designed to slow or prevent Alzheimer’s-related cognitive decline before visible symptoms appear.
Several clinical trials are already studying whether disease-modifying therapies can benefit people with biological signs of Alzheimer’s disease but who do not yet have cognitive impairment. If these treatments prove effective, blood biomarkers such as p-tau217 could help identify individuals most likely to benefit from early intervention.
Such an approach could potentially bring Alzheimer’s disease prevention closer to cardiovascular prevention, in which cholesterol measurements help doctors estimate future heart attack risk and determine who might benefit from treatment.
For now, the blood test offers researchers a way to identify people at higher risk who might be suitable candidates for prevention studies.
“Today, p-tau217 may help identify people at high risk for future Alzheimer’s-related dementia and participate in prevention trials,” Sperling said. “As these trials progress, individualized estimates, including biomarker prognostic value, could guide earlier treatment and monitoring decisions.”
Paternity: In addition to Sperling and Buckley, Mass General Brigham authors include Diana L. Townsend, Colin J. Birkenbihl, Madison Cuppels, Gillian T. Coughlan, Mabel T. Seto, Jane A. Brown, Michael J. Properzi, Merle C. Hönig, Annie Li, Aaron P. Schultz, Jasmeer Chhatwal, Hyun-Sik Yang, Steven Arnold, Pia Kivisäkk, Brian Healy, Jorge Garcia Condado, Wai-Ying Wendy Yau, Michelle Farrell, Rebecca E. Amariglio, Dorene M. Rentz, Kathryn V. Papp, and Keith A. Johnson. Other authors include Bryan D. James, Sid O’Bryant, Robert A. Rissman, Melissa Petersen, Jessica ZK Caldwell, Tobey Betthauser, Julie Elisabeth Oomens, Maria Carrigan, Sterling C. Johnson, Oliver Langford, Ron Brookmeyer, Timothy J. Hohman, Michael Donohue, and Paul S. Aisen.
Disclosures: Buckley reported receiving grants from the National Institutes of Health (NIH) outside the submitted work. Sperling reported receiving grants from the NIH (A4; R01 AG063689, U24AG057437), the GHR Foundation, and the 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 funding of public-private partnership clinical trials by Eisai and Eli Lilly outside of the submitted work. Additional information about the author is available in the JAMA disclosures section of the document.
Funding: This study received partial funding from the National Institutes of Health (R01AG079142, DP2AG082342, U01 AG024904, R01AG054073, R01AG058533, R01AG070862, P41EB015922, U19AG078109, R01AG027161, U.S. Department of Defense (W81XWH-12-2-0012), Eli Lilly, the Alzheimer’s Association, Accelerating Medicines Partnership, the GHR Foundation, an anonymous foundation, and private donors. Additional in-kind support was provided by Avid, Cogstate, Albert Einstein College of Medicine, Foundation for Neurologic Diseases, and Meso Scale Diagnostics.
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