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