ALZHEIMER’S disease (AD) symptom onset was predicted within a margin of just a few years using plasma p-tau217 clock models, according to new longitudinal research.
Predicting not only whether, but when, cognitively unimpaired individuals will develop symptomatic AD has remained a major challenge. Although amyloid and tau positron emission tomography–based clock models have previously shown promise, these imaging approaches are costly and not widely accessible. A blood-based biomarker model could therefore offer a more scalable alternative for use in clinical trials and, potentially, future clinical practice.
Plasma Clocks Estimate Timing of Alzheimer’s Disease
Researchers analysed longitudinal plasma percentage phosphorylated tau at position 217 (%p-tau217), defined as the ratio of phosphorylated to non-phosphorylated tau at position 217, in two independent cohorts (n=258 and n=345). Using these repeated measurements, they constructed clock models to estimate the age at which individuals became plasma %p-tau217 positive.
The estimated age at plasma %p-tau217 positivity was significantly associated with the age at onset of AD symptoms. The models demonstrated adjusted R² values ranging from 0.337–0.612, with a median absolute error of 3.0–3.7 years between predicted and observed symptom onset.
Importantly, the interval between plasma %p-tau217 positivity and development of symptomatic Alzheimer’s disease was markedly shorter in older individuals, indicating that age influenced the tempo from biomarker positivity to clinical manifestation.
Consistent Findings Across Assays
To assess robustness, the investigators constructed similar clock models using data from one p-tau217/Aβ42 immunoassay and four additional plasma p-tau217 immunoassays. These models yielded comparable findings, supporting the reproducibility of plasma p-tau217–based timing estimates across different assay platforms.
The authors concluded that the time until onset of Alzheimer’s disease symptoms could be estimated using a single blood test within a margin of error that may be acceptable for use in clinical trials.
While further validation will be required, these findings suggest that plasma p-tau217 clocks could provide a practical and accessible tool to estimate the timing of symptomatic Alzheimer’s disease, advancing efforts to refine enrolment strategies and staging in prevention-focused research.
Reference
Petersen KK et al. Predicting onset of symptomatic Alzheimer’s disease with plasma p-tau217 clocks. Nat Med. 2026; doi:10.1038/s41591-026-04206-y.
