Abstract
BackgroundExosomes, 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.ResultsWe 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.ConclusionsThese data suggest that exosomes can counteract the inhibitory action of Aβ, which contributes to perpetual capability for synaptic plasticity.
Highlights
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)
Exosomes attenuated Aβ-derived diffusible ligand (ADDL)-mediated long-term potentiation (LTP) inhibition We investigated whether exosomes affect Aβ-induced LTP impairment in the CA1 region of the dorsal hippocampus in vivo
Our characterization of ADDLs revealed the presence of a heterogeneous mixture of different Aβ species, some of which were at least partially stable in SDS and which existed as small globular structures of 3 - 6 nm [5,19]
Summary
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. To examine the mechanisms that underlie the synaptic dysfunction caused by Aβ oligomers, several laboratories have utilized a cellular correlate of learning and memory long-term potentiation (LTP) - and have studied the effectiveness of different forms of soluble Aβ preparations including Aβ-derived diffusible ligands (ADDLs) and AD brain-derived Aβ [4,5,6,7]. Exosomes have been proposed to exert multiple physiological roles [13] and are known to contain machinery to synthesize, degrade and induce aggregation of Aβ [14,15,16], whether these factors in exosomes increase or decrease the deleterious actions of Aβ is a matter of debate [15,16,17,18]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
