Exosomes neutralize synaptic-plasticity-disrupting activity of Aß assemblies in vivo.
Item Type:Journal Article
Citation:An K, Klyubin I, Kim Y, Jung JH, Mably AJ, O'Dowd ST, Lynch T, Kanmert D, Lemere CA, Finan GM, Park JW, Kim TW, Walsh DM, Rowan MJ, Kim JH, Exosomes neutralize synaptic-plasticity-disrupting activity of Aß assemblies in vivo., Molecular brain, 6, 2013, 47
1756-6606-6-47.pdf (PDF) 1.234Mb
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 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.
Science Foundation Ireland (SFI)
Grant Agreement MEMOLOAD 201159
European Union (EU)
Type of material:Journal Article
Series/Report no:Molecular brain
Availability:Full text available