A blood test for the biomarker phosphorylated tau-217 (p-tau217) recently received federal approval, but questions have been raised about how accurately such a test can predict whether cognitively healthy people will develop cognitive impairment, a key symptom of Alzheimer’s disease. A new international study led by experts at the Massachusetts General Brigham Neuroscience Institute and involving researchers on three continents is shedding new light on the prognostic value of these tests. The study found that individuals without cognitive impairment with very high levels of the biomarker had a 38% absolute risk of developing cognitive impairment over the next five years, and an even higher risk over the next 10 years. Results will be presented at the Alzheimer’s Disease Association International Conference and published at the same time. Japan Automobile Manufacturers Association.
There are still no disease-modifying treatments for people found to be at high risk of developing cognitive impairment due to Alzheimer’s disease. Therefore, currently available blood tests are not recommended for asymptomatic people. Today, regardless of test results, the medical advice remains: exercise regularly, maintain a healthy diet, and prioritize sleep and overall health. But the landscape of preventive care could change rapidly if ongoing trials of disease-modifying therapies prove effective. In the future, these tests may help identify those who may benefit most from these treatments. Our long-term goal is to get to the point where cholesterol tests can predict heart attack risk. ”
Dr. Leisa Sperling, Senior and corresponding author; Neurologist at Massachusetts General Brigham Neuroscience Institute
To conduct the study, researchers pooled data from six observational studies and clinical trials based in North America, Japan, and Australia. The study involved 2,684 older adults without cognitive impairment. Blood samples were tested for p-tau217 levels, and PET imaging was performed to obtain baseline readings when participants enrolled in the study. Participants were followed up annually to assess cognitive function. The earliest enrollment in any study was in 2004, and the most recent follow-up was in 2025.
The research team graphed the participants’ cognitive trajectories and quantified their risk of developing cognitive impairment over time. Approximately 478 participants progressed to cognitive impairment. Higher p-tau217 levels at baseline were significantly associated with cognitive impairment. People with very high p-tau217 levels had a 38% risk of developing cognitive impairment over five years. This risk increased over time, reaching 78% over 10 years. However, data were much sparser on outcomes after 10 years.
“This is an important step toward better understanding what p-tau217 tells us about a person’s risk for cognitive impairment,” said lead author Dr. 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.”
Researchers found that the blood test could predict risk independent of other known risk factors, such as amyloid beta plaques that can show up on PET scans and known genetic risk factors (such as APOE4). Although this study design has many strengths, it is still limited by selection bias and focuses on relatively short-term risks rather than lifelong risks. Future research is needed to validate the findings in a broader and more representative population. By following participants over time, researchers can further refine individual risk estimates.
“Now, p-tau217 can help identify people at high risk of developing Alzheimer’s disease in the future to participate in prevention trials,” Sperling said. “As these trials progress, individualized estimates, including the prognostic value of the biomarkers, may help inform earlier treatment and monitoring decisions.”
sauce:
Reference magazines:
Buckley, R.F.; Others. (2026) Prognostic value of blood-based P-tau 217 levels for progression to cognitive impairment. jam. DOI: 10.1001/jama.2026.12556. https://jamanetwork.com/journals/jama/fullarticle/2851720
