Long-term depression links amyloid-β to the pathological hyperphosphorylation of tau.

ABSTRACT: In Alzheimer's disease, soluble oligomers of the amyloid-β peptide (Aβ_o) trigger a cascade of events that includes abnormal hyperphosphorylation of the protein tau, which is essential for pathogenesis. However, the mechanistic link between these two key pathological proteins remains unclear. Using hippocampal slices, we show here that an Aβ_o-mediated increase in glutamate release probability causes enhancement of synaptically evoked N-methyl-d-aspartate subtype glutamate receptor (NMDAR)-dependent long-term depression (LTD). We also find that elevated glutamate release probability is required for Aβ_o-induced pathological hyperphosphorylation of tau, which is likewise NMDAR dependent. Finally, we show that chronic, repeated chemical or optogenetic induction

SUBMITTER: Taylor HBC 

PROVIDER: S-EPMC8424646 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature