Predicting onset of symptomatic Alzheimer's disease with plasma p-tau217 clocks
Summary
Predicting not just if, but also when, cognitively unimpaired individuals are likely to develop onset of Alzheimer's disease (AD) symptoms would be useful to clinical trials and, eventually, clinical practice. Although clock models based on amyloid and tau positron emission tomography have shown promise in predicting the onset of AD symptoms, a model based on plasma biomarkers would be more accessible. Using longitudinal plasma %p-tau217 (the ratio of phosphorylated to non-phosphorylated t
Content
# Predicting onset of symptomatic Alzheimer's disease with plasma p-tau217 clocks
*Published: 2026 Mar*
Predicting not just if, but also when, cognitively unimpaired individuals are
likely to develop onset of Alzheimer's disease (AD) symptoms would be useful to
clinical trials and, eventually, clinical practice. Although clock models based
on amyloid and tau positron emission tomography have shown promise in predicting
the onset of AD symptoms, a model based on plasma biomarkers would be more
accessible. Using longitudinal plasma %p-tau217 (the ratio of phosphorylated to
non-phosphorylated tau at position 217) from two independent cohorts (n = 258
and n = 345), clock models were used to estimate the age at plasma %p-tau217
positivity. The estimated age at plasma %p-tau217 positivity was associated with
the age at onset of AD symptoms (adjusted R2 of 0.337-0.612) with a median
absolute error of 3.0-3.7 years. Notably, the time from %p-tau217 positivity to
onset of AD symptoms was markedly shorter in older individuals. Similar models
were constructed with data from one p-tau217/Aβ42 immunoassay and four plasma
p-tau217 immunoassays. These findings suggest that the time until onset of AD
symptoms can be estimated using a single blood test within a margin of error
that is acceptable for use in clinical trials.
DOI: 10.1038/s41591-026-04206-y