Blood Biomarker May Signal Cognitive Decline Risk a Decade Before Symptoms

Earlier risk stratification could improve monitoring and support enrollment in prevention studies before symptoms emerge. Blood-based biomarkers are being explored to help fill this gap. A new study shows that a plasma assay for phosphorylated tau 217 (p-tau217) can estimate long-term risk of cognitive decline in symptom-free adults.

The Alzheimer’s Association detailed these findings at the Alzheimer’s Association International Conference (AAIC) 2026, with simultaneous publication in JAMA. The study focused on a blood test that quantifies p-tau217 to estimate future risk of cognitive impairment. Phosphorylated tau 217 is a modified form of tau, and tau tangles are a hallmark of Alzheimer’s disease closely linked to cognitive decline. The biomarker is also strongly associated with beta amyloid, another hallmark of Alzheimer’s disease, and in this study provided predictive information beyond brain imaging and genetics.

Investigators analyzed data from nearly 2,700 cognitively unimpaired adults, with an average age of 70, drawn from six major Alzheimer’s research groups and clinical trials. Participants were cognitively healthy at the time of blood draw and were followed for an average of nearly five years, with some followed for more than a decade. Cognitive outcomes were tracked using standard assessments of memory, thinking, and daily functioning, while statistical models estimated the likelihood of decline over two, five, and 10 years.

Higher blood p-tau217 concentrations predicted faster decline, with the strongest effects seen in individuals who also showed elevated amyloid beta on positron emission tomography (PET). Among cognitively healthy older adults with very high p-tau217 levels, defined as more than twice the study average, the estimated likelihood of progressing to cognitive impairment was approximately 38% within five years and 78% within 10 years. Cognitive impairment was defined as mild cognitive impairment (MCI), dementia, or a consecutive Clinical Dementia Rating (CDR) of 0.5. Those with moderately elevated levels had estimated risks of about 15% at five years and 45% at 10 years.

Researchers cautioned that p-tau217 alone cannot fully predict individual risk, as factors such as age, genetics, kidney function, obesity, and racial and ethnic background can influence biomarker levels and dementia risk. More diverse cohorts with longer follow-up are needed to refine these estimates.

“Our findings provide some of the clearest evidence yet that elevated p‑tau217 levels may help detect dementia risk years earlier — even in adults with no noticeable memory or thinking problems. Once verified, these blood tests could be used to recruit patients for clinical trials of treatments to prevent cognitive decline and dementia. In the future, when treatments are approved for use early in the disease process, these tests could help guide monitoring, treatment decisions and counseling for patients and families,” said Rachel F. Buckley, Ph.D., lead author and associate chair of research in the Mass General Brigham Neuroscience Institute, and associate professor of neurology, Harvard Medical School, Boston.

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