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dc.creatorSánchez Varo, Raquel Maríaes
dc.creatorTrujillo Estrada, Laura Isabeles
dc.creatorSánchez Mejías, Elisabethes
dc.creatorTorres Canalejo, Manueles
dc.creatorBaglietto Vargas, Davides
dc.creatorMoreno González, Inéses
dc.creatorJiménez Muñoz, Sebastiánes
dc.creatorRuano Caballero, Diegoes
dc.creatorVizuete Chacón, María Luisaes
dc.creatorVitorica Ferrández, Francisco Javieres
dc.creatorGutiérrez Pérez, Antoniaes
dc.date.accessioned2022-08-12T10:00:44Z
dc.date.available2022-08-12T10:00:44Z
dc.date.issued2012
dc.identifier.citationSánchez Varo, R.M., Trujillo Estrada, L.I., Sánchez Mejías, E., Torres Canalejo, M., Baglietto Vargas, D., Moreno González, I.,...,Gutiérrez Pérez, A. (2012). Abnormal accumulation of autophagic vesicles correlates with axonal and synaptic pathology in young Alzheimer’s mice hippocampus. Acta Neuropathologica, 123 (1), 53-70.
dc.identifier.issn0001-6322es
dc.identifier.issn1432-0533es
dc.identifier.urihttps://hdl.handle.net/11441/136176
dc.description.abstractDystrophic neurites associated with amyloid plaques precede neuronal death and manifest early in Alzheimer’s disease (AD). In this work we have characterized the plaque-associated neuritic pathology in the hippocampus of young (4- to 6-month-old) PS1M146L/ APP751SL mice model, as the initial degenerative process underlying functional disturbance prior to neuronal loss. Neuritic plaques accounted for almost all fibrillar deposits and an axonal origin of the dystrophies was demonstrated. The early induction of autophagy pathology was evidenced by increased protein levels of the autophagosome marker LC3 that was localized in the axonal dystrophies, and by electron microscopic identification of numerous autophagic vesicles filling and causing the axonal swellings. Early neuritic cytoskeletal defects determined by the presence of phosphorylated tau (AT8-positive) and actin–cofilin rods along with decreased levels of kinesin-1 and dynein motor proteins could be responsible for this extensive vesicle accumulation within dystrophic neurites. Although microsomal Ab oligomers were identified, the presence of A11-immunopositive Ab plaques also suggested a direct role of plaque-associated Ab oligomers in defective axonal transport and disease progression. Most importantly, presynaptic terminals morphologically disrupted by abnormal autophagic vesicle buildup were identified ultrastructurally and further supported by synaptosome isolation. Finally, these early abnormalities in axonal and presynaptic structures might represent the morphological substrate of hippocampal dysfunction preceding synaptic and neuronal loss and could significantly contribute to AD pathology in the preclinical stages.es
dc.description.sponsorshipFondo de Investigación Sanitaria (FIS). Instituto de Salud Carlos III, España. PS09/00099, PS09/00151, PS09/00848 y PS09/00376es
dc.description.sponsorshipJunta de Andalucía. SAS P09/496 y CTS-4795es
dc.formatapplication/pdfes
dc.format.extent18 p.es
dc.language.isoenges
dc.publisherSpringeres
dc.relation.ispartofActa Neuropathologica, 123 (1), 53-70.
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectPS1/APP transgenic micees
dc.subjectDystrophic neuriteses
dc.subjectElectron microscopyes
dc.subjectLC3es
dc.subjectAmyloid plaqueses
dc.subjectPresynaptic terminalses
dc.titleAbnormal accumulation of autophagic vesicles correlates with axonal and synaptic pathology in young Alzheimer’s mice hippocampuses
dc.typeinfo:eu-repo/semantics/articlees
dcterms.identifierhttps://ror.org/03yxnpp24
dc.type.versioninfo:eu-repo/semantics/publishedVersiones
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Bioquímica y Biología Moleculares
dc.relation.projectIDPS09/00099es
dc.relation.projectIDPS09/00151es
dc.relation.projectIDPS09/00848es
dc.relation.projectIDPS09/00376es
dc.relation.projectIDSAS P09/496es
dc.relation.projectIDCTS-4795es
dc.relation.publisherversionhttps://doi.org/10.1007/s00401-011-0896-xes
dc.identifier.doi10.1007/s00401-011-0896-xes
dc.journaltitleActa Neuropathologicaes
dc.publication.volumen123es
dc.publication.issue1es
dc.publication.initialPage53es
dc.publication.endPage70es
dc.identifier.sisius20035813es
dc.contributor.funderInstituto de Salud Carlos IIIes
dc.contributor.funderJunta de Andalucíaes

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