Exosomes neutralize synaptic-plasticity-disrupting activity of A? assemblies in vivo.

ABSTRACT: BACKGROUND: Exosomes, small extracellular vesicles of endosomal origin, have been suggested to be involved in both the metabolism and aggregation of Alzheimer's disease (AD)-associated amyloid ?-protein (A?). Despite their ubiquitous presence and the inclusion of components which can potentially interact with A?, the role of exosomes in regulating synaptic dysfunction induced by A? has not been explored. RESULTS: We here provide in vivo evidence that exosomes derived from N2a cells or human cerebrospinal fluid can abrogate the synaptic-plasticity-disrupting activity of both synthetic and AD brain-derived A?. Mechanistically, this effect involves sequestration of synaptotoxic A? assemblies by exosomal surface proteins such as PrPC rather than A? proteolysis. CONCLUSIONS: These data suggest that exosomes can counteract the inhibitory action of A?, which contributes to perpetual capability for synaptic plasticity.

SUBMITTER: An K 

PROVIDER: S-EPMC4222117 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature