Amyloid β-protein oligomers promote the uptake of tau fibril seeds potentiating intracellular tau aggregation.

ABSTRACT:

Background

Repeated failure of drug candidates targeting Alzheimer's disease (AD) in clinical trials likely stems from a lack of understanding of the molecular mechanisms underlying AD pathogenesis. Recent research has highlighted synergistic interactions between aggregated amyloid-β (Aβ) and tau proteins in AD, but the molecular details of how these interactions drive AD pathology remain elusive and speculative.

Methods

Here, we test the hypothesis that Aβ potentiates intracellular tau aggregation, and show that oligomeric Aβ specifically exacerbates proteopathic seeding by tau. Using tau-biosensor cells, we show that treatment with sub-toxic concentrations of Aβ oligomers, but not monomers or fibrils, "primes" cells, making them more susceptible to tau seeding. The treatme

SUBMITTER: Shin WS 

PROVIDER: S-EPMC6800506 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature