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

Kyongman An, Igor Klyubin, Youngkyu Kim, Jung Hoon Jung, Alexandra J. Mably, Sean T. O'Dowd, Timothy Lynch, Daniel Kanmert, Cynthia A. Lemere, Gina M. Finan, Joon Won Park, Tae Wan Kim, Dominic M. Walsh, Michael J. Rowan, Joung Hun Kim

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

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 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 PrP C 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.

Original languageEnglish (US)
Article number47
JournalMolecular Brain
Volume6
Issue number1
DOIs
StatePublished - 2013
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Exosomes
  • PrP
  • Synaptic plasticity

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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