Background

Diagnostic methods available for in vivo diagnosis of Alzheimer’s disease are expensive and invasive. Plasma measured tau phosphorylated at threonine 217 (p-tau217) is one potential non-invasive biomarker of Alzheimer’s disease. We tested whether baseline plasma p-tau217 is associated with subsequent cognition and PET-measured pathology in non-demented carriers from the world’s largest known autosomal dominant Alzheimer’s disease kindred due to a single mutation.

Methods

Participants included 44 presenilin-1 E280A carriers (n=24) and non-carrier family members (n=20) recruited from the COLBOS (Colombia-Boston) longitudinal biomarker study. Outcomes included baseline plasma p-tau217 and its associations with cortical β-amyloid-PET, tau-PET, and word list delayed recall measured 7.61 years later.

Results

Plasma p-tau217 was higher in carriers than non-carriers (p=.005). Plasma p-tau217 correlated with subsequent PET-pathology, including cortical β-amyloid (r=0.55, p<.001) and regional tau (inferior temporal cortex: r=0.44, p=.003; entorhinal cortex: r=0.47, p=.001; precuneus: r=0.53, p<.001). Higher plasma p-tau217 correlated with lower subsequent delayed recall (r =-0.52, p<.001).

Conclusions

Our findings suggest that baseline levels of plasma p-tau217 predict subsequent brain pathological burden and cognition in presenilin-1 E280A carriers. These results provide support for plasma p-tau217 as a minimally invasive diagnostic and prognostic biomarker for Alzheimer’s disease, with potential utility in clinical practice and trials.