Kyongman An 1 , Igor Klyubin 2 , Youngkyu Kim 3 , Jung Hoon Jung 1 , Alexandra J Mably 4 , 5 , Sean T O’Dowd 5 , 6 , Timothy Lynch 6 , Daniel Kanmert 4 , Cynthia A Lemere 4 , Gina M Finan 7 , Joon Won Park 3 , Tae-Wan Kim 7 , Dominic M Walsh 4 , Michael J Rowan 2 , Joung-Hun Kim , 1
13 November 2013
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 β-protein (Aβ). Despite their ubiquitous presence and the inclusion of components which can potentially interact with Aβ, the role of exosomes in regulating synaptic dysfunction induced by Aβ has not been explored.
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 Aβ. Mechanistically, this effect involves sequestration of synaptotoxic Aβ assemblies by exosomal surface proteins such as PrP C rather than Aβ proteolysis.