Blood test p-tau217 predicts up to 38% risk of cognitive impairment within five years
A multinational study found that very high levels of the blood-based biomarker p-tau217 are linked to a 38% absolute risk of cognitive impairment over five years, independent of amyloid PET findings and APOE4 status.
Researchers from the Mass General Brigham Neuroscience Institute and collaborators across North America, Japan and Australia reported that plasma phosphorylated tau 217 (p-tau217) can forecast the likelihood of cognitive decline in older adults who are currently cognitively normal. An analysis of 2,684 participants from six longitudinal cohorts showed that individuals with "very high" baseline p-tau217 levels faced a 38% absolute risk of developing mild cognitive impairment or dementia within five years, rising to 78% over ten years.
The risk estimates remained significant after adjusting for amyloid-beta plaque burden measured by PET scans and for the presence of the APOE4 allele, indicating that p-tau217 provides prognostic information independent of these established risk factors. Each standard-deviation increase in p-tau217 was associated with a 38% higher hazard of progression, and higher levels also correlated with faster decline on the Preclinical Alzheimer Cognitive Composite.
"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," said Dr. Reisa Sperling, senior author and neurologist at Mass General Brigham.
"Today, our medical advice would remain the same regardless of test results: exercise regularly, maintain a healthy diet, and prioritize sleep and overall wellness," Sperling added.
The investigators suggest that, while routine screening is not advised at present, p-tau217 could become a tool for identifying candidates for preventive clinical trials and, eventually, a screening measure analogous to cholesterol testing for heart disease. The study’s authors note limitations including selection bias and relatively sparse data for outcomes beyond ten years, and they call for validation in broader, population-based samples before the test can be used for individual prognosis in clinical practice.