Exosomes neutralize synaptic-plasticity-disrupting activity of Aβ assemblies in vivo

An, Kyongman; Klyubin, Igor; Kim, Youngkyu; Jung, Jung; Mably, Alexandra; O’Dowd, Sean; Lynch, Timothy; Kanmert, Daniel; Lemere, Cynthia; Finan, Gina M.; Park, Joon; Kim, Tae-Wan; Walsh, Dominic; Rowan, Michael; Kim, Joung-Hun

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 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. 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 Aβ. Mechanistically, this effect involves sequestration of synaptotoxic Aβ assemblies by exosomal surface proteins such as PrPC rather than Aβ proteolysis. Conclusions: These data suggest that exosomes can counteract the inhibitory action of Aβ, which contributes to perpetual capability for synaptic plasticity.


  • thumnail for 1756-6606-6-47-S1.docx 1756-6606-6-47-S1.docx application/vnd.openxmlformats-officedocument.wordprocessingml.document 60.4 KB Download File

Also Published In

Molecular Brain

More About This Work

Academic Units
Biological Sciences
Pathology and Cell Biology
Published Here
September 10, 2014