PAC1 receptor-mediated clearance of tau in postsynaptic compartments attenuates tau pathology in mouse brain.

ABSTRACT: Accumulation of pathological tau in synapses has been identified as an early event in Alzheimer's disease (AD) and correlates with cognitive decline in patients with AD. Tau is a cytosolic axonal protein, but under disease conditions, tau accumulates in postsynaptic compartments and presynaptic terminals, due to missorting within neurons, transsynaptic transfer between neurons, or a failure of clearance pathways. Using subcellular fractionation of brain tissue from rTg4510 tau transgenic mice with tauopathy and human postmortem brain tissue from patients with AD, we found accumulation of seed-competent tau predominantly in postsynaptic compartments. Tau-mediated toxicity in postsynaptic compartments was exacerbated by impaired proteasome activity detected by measuring lysine-48 polyubiquit

SUBMITTER: Schaler AW 

PROVIDER: S-EPMC8988215 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature