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

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 ß-protein (Aß). Despite their ubiquitous presence and the inclusion of components which can potentially interact with Aß, the role of exosomes in regulating synaptic dysfunction induced by Aß 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 Aß. Mechanistically, this effect involves sequestration of synaptotoxic Aß assemblies by exosomal surface proteins such as PrPC rather than Aß proteolysis. CONCLUSIONS: These data suggest that exosomes can counteract the inhibitory action of Aß, which contributes to perpetual capability for synaptic plasticity.