Abstract
Alzheimer’s disease (AD) is an age-related neurodegenerative disorder in which aggregation-prone neurotoxic amyloid β-peptide (Aβ) accumulates in the brain. Extracellular vesicles (EVs), including exosomes, are small 50–150 nm membrane vesicles that have recently been implicated in the prion-like spread of self-aggregating proteins. Here we report that EVs isolated from AD patient cerebrospinal fluid and plasma, from the plasma of two AD mouse models, and from the medium of neural cells expressing familial AD presenilin 1 mutations, destabilize neuronal Ca2+ homeostasis, impair mitochondrial function, and sensitize neurons to excitotoxicity. EVs contain a relatively low amount of Aβ but have an increased Aβ42/ Aβ40 ratio; the majority of Aβ is located on the surface of the EVs. Impairment of lysosome function results in increased generation of EVs with elevated Aβ42 levels. EVs may mediate transcellular spread of pathogenic Aβ species that impair neuronal Ca2+ handling and mitochondrial function, and may thereby render neurons vulnerable to excitotoxicity.
Document Type
Article
Publication Date
9-22-2016
Digital Object Identifier (DOI)
https://doi.org/10.1038/npjamd.2016.19
Funding Information
This research was supported by the Intramural Research Program of the National Institute on Aging (NIA), and by an NIA grant supporting the University of Kentucky Alzheimer’s Disease Research Center (P30-AG0-28383).
Repository Citation
Eitan, Erez; Hutchison, Emmette R.; Marosi, Krisztina; Comotto, James; Mustapic, Maja; Nigam, Saket M.; Suire, Caitlin; Maharana, Chinmoyee; Jicha, Gregory A.; Liu, Dong; Machairaki, Vasiliki; Witwer, Kenneth W.; Kapogiannis, Dimitrios; and Mattson, Mark P., "Extracellular Vesicle-Associated Aβ Mediates Trans-Neuronal Bioenergetic and Ca2+-Handling Deficits in Alzheimer's Disease Models" (2016). Sanders-Brown Center on Aging Faculty Publications. 74.
https://uknowledge.uky.edu/sbcoa_facpub/74
Supplementary Information: Supplementary Figures
Included in
Family, Life Course, and Society Commons, Geriatrics Commons, Neuroscience and Neurobiology Commons
Notes/Citation Information
Published in npj Aging and Mechanisms of Disease, v. 2, article no. 16019, p. 1-11.
© The Author(s) 2016
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