A blood test measuring a biomarker linked to Alzheimer’s disease may help identify older adults at elevated risk of cognitive decline years before noticeable problems with memory and thinking appear. In an international study of 2,684 older adults with no cognitive impairment at enrollment, participants with very high levels of phosphorylated tau-217 (p-tau217) had an estimated 38% chance of developing cognitive impairment within five years and a 78% chance within 10 years. However, the researchers noted that substantially less data were available for the longer-term estimate.
The findings offer new evidence that blood tests could help predict future cognitive problems in people who currently show no symptoms. Scientists at the Massachusetts General Brigham Neuroscience Institute led the study, which involved research teams across North America, Japan and Australia. The results were presented at the Alzheimer’s Association International Conference and published simultaneously in a scientific journal.
Tracking Alzheimer’s risk with a blood biomarker
The study focused on p-tau217, a blood biomarker associated with Alzheimer’s disease. A test that measures p-tau217 recently received federal approval, raising hopes that blood tests could make Alzheimer’s detection easier. Important questions remain, however, including whether these tests can reliably predict which cognitively healthy people will eventually develop symptoms.
To investigate, researchers combined data from six observational studies and clinical trials involving 2,684 older adults who showed no signs of cognitive impairment when they joined the studies.
At enrollment, participants provided blood samples for p-tau217 analysis. They also underwent positron emission tomography (PET) brain scans, which allowed researchers to establish baseline measures of brain health. Annual follow-up assessments tracked changes in memory, thinking and other cognitive abilities.
The combined dataset covered an unusually long period. Some participants had joined one of the studies as early as 2004, while the latest follow-up assessment took place in 2025.
Across the studies, approximately 478 participants eventually developed cognitive impairment. Comparing these outcomes with the participants’ initial blood-test results, the researchers found a strong association between elevated p-tau217 levels and the likelihood of future cognitive problems.
Among participants with very high biomarker levels, the estimated probability of developing cognitive impairment within five years was 38%. After 10 years, the estimated probability rose to 78%. The researchers emphasized that significantly fewer observations were available beyond the 10-year point, making the long-term predictions less reliable.
Predictive value beyond genetics and brain scans
One of the study’s key findings was that p-tau217 provided information about future cognitive decline beyond other established risk factors.
Even after the researchers accounted for amyloid-beta plaques—abnormal protein deposits in the brain that can be detected with PET scans—p-tau217 remained significantly associated with cognitive impairment. Its predictive value also extended beyond known genetic risk factors such as APOE4.
The results suggest that a relatively simple blood test could eventually give doctors additional information when estimating an individual’s likelihood of developing cognitive impairment.
“This is an important step toward better understanding what p-tau217 can tell us about risk for cognitive impairment,” said lead author Rachel F. Buckley, a cognitive neuroscientist at the Massachusetts General Brigham Neuroscience Institute. “What really sets this study apart is that it estimates an individual’s level of risk for cognitive impairment. We harmonized the data across six cohorts, creating a large and diverse dataset, and yet we found consistent results that show how p-tau217 signals risk over time.”
Rather than simply identifying biological changes associated with Alzheimer’s disease, the study helps estimate how those changes translate into the probability of developing symptoms over a specified period.
Why routine testing is not yet recommended for healthy people
Despite the promising findings, researchers caution that blood tests are not currently recommended for routine Alzheimer’s disease risk screening in people without symptoms.
One reason is that preventive treatments capable of changing the course of the disease have not yet been established for healthy people identified as being at high risk.
“There are still no disease-modifying treatments for people found to be at high risk of developing cognitive impairment from Alzheimer’s disease, so we do not recommend currently available blood tests for people who are asymptomatic,” said senior corresponding author Leisa Sperling, M.D., a neurologist at Massachusetts General Brigham Neuroscience. “Currently, our medical advice is the same regardless of test results: exercise regularly, maintain a healthy diet, and prioritize sleep and overall health.”
“However, the landscape of preventive care could change rapidly if ongoing trials of disease-modifying therapies prove beneficial,” Sperling added. “In the future, these tests could help identify patients who are most likely to benefit from these treatments. Our long-term goal is to get to the point where cholesterol tests predict heart attack risk.”
The study has several limitations. Although the researchers combined data from multiple studies and geographic regions, the participants may not fully represent the broader population. This potential selection bias could affect how well the findings apply to other groups.
The analysis also focused on predicting cognitive impairment over a relatively limited period rather than estimating a person’s lifetime risk. Larger and more representative studies, along with longer follow-up periods, will be needed to confirm the findings and improve the accuracy of individual risk estimates.
Could blood tests support Alzheimer’s prevention?
The greatest potential benefit of this approach could emerge as scientists develop treatments intended to slow or prevent Alzheimer’s-related cognitive decline before noticeable symptoms begin.
Several clinical trials are investigating whether disease-modifying therapies can help people who have biological signs of Alzheimer’s disease but no cognitive impairment. If these treatments prove effective, blood biomarkers such as p-tau217 could help identify the people most likely to benefit from early intervention.
Such an approach could eventually bring Alzheimer’s 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, blood tests offer researchers a way to identify people at elevated risk who may be suitable candidates for prevention studies.
“Now, p-tau217 can help identify people at high risk of future Alzheimer’s dementia for participation in prevention trials,” Sperling said. “As these trials progress, individualized estimates, including the prognostic value of the biomarkers, may guide earlier treatment and monitoring decisions.”
Authors, disclosures and funding
In addition to Sperling and Buckley, the Mass General Brigham authors include Diana L. Townsend, Colin J. Birkenbiel, Madison Kuppels, Gillian T. Coughlan, Mabel T. Seto, Jane A. Brown, Michael J. Properzi, Merle C. Honig, Annie Lee, Aaron P. Schulz, Jasmia Chatwal, Hyungsik Yang, Steven Arnold, Pia Kivisak, Brian Healy, Jorge Garcia Condado, Waiying Wendy Yau, Michelle Farrell, Rebecca E. Amarillio, Doren M. Lentz, Kathryn V. Papp and Keith A. Johnson. Additional authors include Brian D. James, Sid O’Bryant, Robert A. Risman, Melissa Petersen, Jessica ZK Caldwell, Toby Betthauser, Julie Elizabeth Omens, Maria Carrigan, Sterling C. Johnson, Oliver Langford, Ron Brookmeyer, Timothy J. Homan, Michael Donahue and Paul S. Eisen.
Buckley reported receiving grants from the National Institutes of Health (NIH) outside the submitted research. Sperling reported receiving grants from the NIH, including A4, R01 AG063689 and U24AG057437, as well as the GHR Foundation and the Alzheimer’s Association during the study. Sperling also reported consulting relationships with AbbVie, AC Immune, Acumen, Alector, Apellis, Biohaven, Bristol Myers Squibb, Ionis, Immunobrain, Janssen, Novo Nordisk, Oligomerix, Prothena, Roche, Therini and Vaxxinity. Outside the submitted research, clinical trial funding will be provided through public-private partnerships with Eisai and Eli Lilly. Additional author disclosures are available in the paper’s disclosure section.
The study was supported by the National Institutes of Health through grants R01AG079142, DP2AG082342, U01 AG024904, R01AG054073, R01AG058533, R01AG070862, P41EB015922, U19AG078109, R01AG027161, R01AG021155, P30AG062715, U19AG010483, R01AG063689 and P01 AG036694, as well as P41EB015896, S10RR021110, S10RR023401 and S10RR023043. Additional in-kind support came from Avid, Cogstate, Albert Einstein College of Medicine, the Neurological Disorders Foundation and Meso Scale Diagnostics.
Source: www.sciencedaily.com
