Introduction: Plasma biomarkers are altered years prior to Alzheimer's disease (AD) clinical onset.
Methods: We measured longitudinal changes in plasma amyloid-beta (Aβ)42/40 ratio, pTau181, pTau231, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) in a cohort of older adults at risk of AD (n = 373 total, n = 229 with Aβ and tau positron emission tomography [PET] scans) considering genetic and demographic factors as possible modifiers of these markers' progression.
Results: Aβ42/40 ratio concentrations decreased, while NfL and GFAP values increased over the 4-year follow-up. Apolipoprotein E (APOE) ε4 carriers showed faster increase in plasma pTau181 than non-carriers. Older individuals showed a faster increase in plasma NfL, and females showed a faster increase in plasma GFAP values. In the PET subsample, individuals both Aβ-PET and tau-PET positive showed faster plasma pTau181 and GFAP increase compared to PET-negative individuals.
Discussion: Plasma markers can track biological change over time, with plasma pTau181 and GFAP markers showing longitudinal change in individuals with preclinical AD.
Highlights: Longitudinal increase of plasma pTau181 and glial fibrillary acidic protein (GFAP) can be measured in the preclinical phase of AD. Apolipoprotein E ε4 carriers experience faster increase in plasma pTau181 over time than non-carriers. Female sex showed accelerated increase in plasma GFAP over time compared to males. Aβ42/40 and pTau231 values are already abnormal at baseline in individuals with both amyloid and tau PET burden.
Keywords: Alzheimer's disease; Aβ; PET; biomarker; pTau; plasma.
© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.