Aβ accumulation causes MVB enlargement and is modelled by dominant negative VPS4A.

ABSTRACT:

Background

Alzheimer's disease (AD)-linked β-amyloid (Aβ) accumulates in multivesicular bodies (MVBs) with the onset of AD pathogenesis. Alterations in endosomes are among the earliest changes associated with AD but the mechanism(s) that cause endosome enlargement and the effects of MVB dysfunction on Aβ accumulation and tau pathology are incompletely understood.

Methods

MVB size and Aβ fibrils in primary neurons were visualized by electron microscopy and confocal fluorescent microscopy. MVB-dysfunction, modelled by expression of dominant negative VPS4A (dnVPS4A), was analysed by biochemical methods and exosome isolation.

Results

Here we show that AD transgenic neurons have enlarged MVBs compared to wild type neurons. Uptake of exogenous Aβ also leads to enlarged MVBs

SUBMITTER: Willen K 

PROVIDER: S-EPMC5569475 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature