Extracellular vesicles: where the amyloid precursor protein carboxyl-terminal fragments accumulate and amyloid-beta oligomerizes

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...

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Autores: Perez-Gonzalez, R, Kim, Y, Miller, C, Pacheco-Quinto, J, Eckman, EA, Levy, E
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p1742
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1742
Access Level:acceso abierto
Palabra clave:A beta oligomers
Alzheimer's disease
APP-CTFs
APP metabolism
exosomes
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spelling Extracellular vesicles: where the amyloid precursor protein carboxyl-terminal fragments accumulate and amyloid-beta oligomerizesPerez-Gonzalez, RKim, YMiller, CPacheco-Quinto, JEckman, EALevy, EA beta oligomersAlzheimer's diseaseAPP-CTFsAPP metabolismexosomesPleiotropic 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-beta 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 alpha- and beta-APP carboxyl-terminal fragments and APP intracellular domain accumulate in EVs over time and amyloid-beta 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.WILEY2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1742FASEB JOURNALISSN: 08926638ISSNe: 15306860reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p17422026-06-14T12:41:47Z
dc.title.none.fl_str_mv Extracellular vesicles: where the amyloid precursor protein carboxyl-terminal fragments accumulate and amyloid-beta oligomerizes
title Extracellular vesicles: where the amyloid precursor protein carboxyl-terminal fragments accumulate and amyloid-beta oligomerizes
spellingShingle Extracellular vesicles: where the amyloid precursor protein carboxyl-terminal fragments accumulate and amyloid-beta oligomerizes
Perez-Gonzalez, R
A beta oligomers
Alzheimer's disease
APP-CTFs
APP metabolism
exosomes
title_short Extracellular vesicles: where the amyloid precursor protein carboxyl-terminal fragments accumulate and amyloid-beta oligomerizes
title_full Extracellular vesicles: where the amyloid precursor protein carboxyl-terminal fragments accumulate and amyloid-beta oligomerizes
title_fullStr Extracellular vesicles: where the amyloid precursor protein carboxyl-terminal fragments accumulate and amyloid-beta oligomerizes
title_full_unstemmed Extracellular vesicles: where the amyloid precursor protein carboxyl-terminal fragments accumulate and amyloid-beta oligomerizes
title_sort Extracellular vesicles: where the amyloid precursor protein carboxyl-terminal fragments accumulate and amyloid-beta oligomerizes
dc.creator.none.fl_str_mv Perez-Gonzalez, R
Kim, Y
Miller, C
Pacheco-Quinto, J
Eckman, EA
Levy, E
author Perez-Gonzalez, R
author_facet Perez-Gonzalez, R
Kim, Y
Miller, C
Pacheco-Quinto, J
Eckman, EA
Levy, E
author_role author
author2 Kim, Y
Miller, C
Pacheco-Quinto, J
Eckman, EA
Levy, E
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv A beta oligomers
Alzheimer's disease
APP-CTFs
APP metabolism
exosomes
topic A beta oligomers
Alzheimer's disease
APP-CTFs
APP metabolism
exosomes
description 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-beta 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 alpha- and beta-APP carboxyl-terminal fragments and APP intracellular domain accumulate in EVs over time and amyloid-beta 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.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1742
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1742
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv WILEY
publisher.none.fl_str_mv WILEY
dc.source.none.fl_str_mv FASEB JOURNAL
ISSN: 08926638
ISSNe: 15306860
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
repository.name.fl_str_mv
repository.mail.fl_str_mv
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