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

INTRODUCTION: 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. METHODS: 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 (A ss) PET, tau PET, plasma p-tau217, p-tau181, and glial fibrillary acidic protein (GFAP) as endpoints. RESULTS: Individual timing of plasma p-tau progression was strongly associated with A ss PET and GFAP progression. In the population, GFAP became abnormal first, then A ss PET, plasma p-tau, and tau PET temporal meta-regions of interest when applying cut points based on young, cognitively unimpaired participants. DISCUSSION: Plasma p-tau is a stronger indicator of a temporally linked response to elevated brain A ss than of tau pathology. While A ss deposition and a rise in GFAP are upstream events associated with tau phosphorylation, the temporal link between p-tau and A ss PET was the strongest.