Astrocyte reactivity influences amyloid-β effects on tau pathology in preclinical Alzheimer's disease.

ABSTRACT: An unresolved question for the understanding of Alzheimer's disease (AD) pathophysiology is why a significant percentage of amyloid-β (Aβ)-positive cognitively unimpaired (CU) individuals do not develop detectable downstream tau pathology and, consequently, clinical deterioration. In vitro evidence suggests that reactive astrocytes unleash Aβ effects in pathological tau phosphorylation. Here, in a biomarker study across three cohorts (n = 1,016), we tested whether astrocyte reactivity modulates the association of Aβ with tau phosphorylation in CU individuals. We found that Aβ was associated with increased plasma phosphorylated tau only in individuals positive for astrocyte reactivity (Ast⁺). Cross-sectional and longitudinal tau-positron emission tomography analyses revealed an A

SUBMITTER: Bellaver B 

PROVIDER: S-EPMC10353939 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature