Modeling the temporal evolution of plasma p-tau in relation to amyloid beta and tau PET

The timing of plasma biomarker changes is not well understood. The goal of this study was to evaluate the temporal co-evolution of plasma and positron emission tomography (PET) Alzheimer's disease (AD) biomarkers.

We included 1408 Mayo Clinic Study of Aging and Alzheimer's Disease Research Center participants. An accelerated failure time (AFT) model was fit with amyloid beta (Aβ) PET, tau PET, plasma p-tau217, p-tau181, and glial fibrillary acidic protein (GFAP) as endpoints.

Individual timing of plasma p-tau progression was strongly associated with Aβ PET and GFAP progression. In the population, GFAP became abnormal first, then Aβ PET, plasma p-tau, and tau PET temporal meta-regions of interest when applying cut points based on young, cognitively unimpaired participants.

Plasma p-tau is a stronger indicator of a temporally linked response to elevated brain Aβ than of tau pathology. While Aβ deposition and a rise in GFAP are upstream events associated with tau phosphorylation, the temporal link between p-tau and Aβ PET was the strongest.

Plasma p-tau progression was more strongly associated with Aβ than tau PET. Progression on plasma p-tau was associated with Aβ PET and GFAP progression. P-tau181 and p-tau217 become abnormal after Aβ PET and before tau PET. GFAP became abnormal first, before plasma p-tau and Aβ PET.