title: Exosomes neutralize synaptic-plasticity-disrupting activity of Aβ assemblies in vivo.
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.
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk 790-784, Korea. joungkim@postech.ac.kr.
authors.forename: Kyongman
authors.initials: K
authors.lastname: An
authors.forename: Igor
authors.initials: I
authors.lastname: Klyubin
authors.forename: Youngkyu
authors.initials: Y
authors.lastname: Kim
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Jung
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Mably
authors.forename: Sean T
authors.initials: ST
authors.lastname: O'Dowd
authors.forename: Timothy
authors.initials: T
authors.lastname: Lynch
authors.forename: Daniel
authors.initials: D
authors.lastname: Kanmert
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Lemere
authors.forename: Gina M
authors.initials: GM
authors.lastname: Finan
authors.forename: Joon Won
authors.initials: JW
authors.lastname: Park
authors.forename: Tae-Wan
authors.initials: TW
authors.lastname: Kim
authors.forename: Dominic M
authors.initials: DM
authors.lastname: Walsh
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rowan
authors.forename: Joung-Hun
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002555:Cerebrospinal Fluid / Q000378:metabolism; D004058:Diffusion; D055354:Exosomes / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D008024:Ligands; D017774:Long-Term Potentiation; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009473:Neuronal Plasticity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D018621:PrPC Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D008024:Ligands; D008565:Membrane Proteins; D018696:Neuroprotective Agents; D018621:PrPC Proteins