Extracellular vesicles : where the amyloid precursor protein carboxyl-terminal fragments accumulate and amyloid-β oligomerizes
Pérez-González, Rocío (Institut d'Investigació Biomèdica Sant Pau)
Kim, Yohan (Nathan Kline Institute for Psychiatric Research (Estats Units d'Amèrica))
Miller, Chelsea (Nathan S. Kline Institute)
Pacheco-Quinto, Javier (Biomedical Research Institute of New Jersey)
Eckman, Elizabeth A. (Biomedical Research Institute of New Jersey)
Levy, Efrat (New York University School of Medicine)
Universitat Autònoma de Barcelona

Fecha:	2020
Resumen:	Pleiotropic roles are proposed for brain extracellular vesicles (EVs) in the development of Alzheimer's disease (AD). Our previous studies have suggested a beneficial role for EVs in AD, where the endosomal system in vulnerable neurons is compromised, contributing to the removal of accumulated material from neurons. However, the involvement of EVs in propagating AD amyloidosis throughout the brain has been considered because the amyloid-β precursor protein (APP), APP metabolites, and key APP cleaving enzymes were identified in association with EVs. Here, we undertook to determine whether the secretase machinery is actively processing APP in EVs isolated from the brains of wild-type and APP overexpressing Tg2576 mice. We found that full-length APP is cleaved in EVs incubated in the absence of cells. The resulting metabolites, both α- and β-APP carboxyl-terminal fragments and APP intracellular domain accumulate in EVs over time and amyloid-β dimerizes. Thus, EVs contribute to the removal from neurons and transport of APP-derived neurotoxic peptides. While this is potentially a venue for propagation of the pathology throughout the brain, it may contribute to efficient removal of neurotoxic peptides from the brain.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Aβ oligomers ; Alzheimer's disease ; APP-CTFs ; APP metabolism ; Exosomes
Publicado en:	FASEB Journal, Vol. 34 Núm. 9 (january 2020) , p. 12922-12931, ISSN 1530-6860

DOI: 10.1096/fj.202000823R
PMID: 32772431

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