dc.creator | Sánchez Varo, Raquel María | es |
dc.creator | Trujillo Estrada, Laura Isabel | es |
dc.creator | Sánchez Mejías, Elisabeth | es |
dc.creator | Torres Canalejo, Manuel | es |
dc.creator | Baglietto Vargas, David | es |
dc.creator | Moreno González, Inés | es |
dc.creator | Jiménez Muñoz, Sebastián | es |
dc.creator | Ruano Caballero, Diego | es |
dc.creator | Vizuete Chacón, María Luisa | es |
dc.creator | Vitorica Ferrández, Francisco Javier | es |
dc.creator | Gutiérrez Pérez, Antonia | es |
dc.date.accessioned | 2022-08-12T10:00:44Z | |
dc.date.available | 2022-08-12T10:00:44Z | |
dc.date.issued | 2012 | |
dc.identifier.citation | Sánchez 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.issn | 0001-6322 | es |
dc.identifier.issn | 1432-0533 | es |
dc.identifier.uri | https://hdl.handle.net/11441/136176 | |
dc.description.abstract | Dystrophic 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.sponsorship | Fondo de Investigación Sanitaria (FIS). Instituto de Salud Carlos III, España. PS09/00099, PS09/00151, PS09/00848 y PS09/00376 | es |
dc.description.sponsorship | Junta de Andalucía. SAS P09/496 y CTS-4795 | es |
dc.format | application/pdf | es |
dc.format.extent | 18 p. | es |
dc.language.iso | eng | es |
dc.publisher | Springer | es |
dc.relation.ispartof | Acta Neuropathologica, 123 (1), 53-70. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | PS1/APP transgenic mice | es |
dc.subject | Dystrophic neurites | es |
dc.subject | Electron microscopy | es |
dc.subject | LC3 | es |
dc.subject | Amyloid plaques | es |
dc.subject | Presynaptic terminals | es |
dc.title | Abnormal accumulation of autophagic vesicles correlates with axonal and synaptic pathology in young Alzheimer’s mice hippocampus | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular | es |
dc.relation.projectID | PS09/00099 | es |
dc.relation.projectID | PS09/00151 | es |
dc.relation.projectID | PS09/00848 | es |
dc.relation.projectID | PS09/00376 | es |
dc.relation.projectID | SAS P09/496 | es |
dc.relation.projectID | CTS-4795 | es |
dc.relation.publisherversion | https://doi.org/10.1007/s00401-011-0896-x | es |
dc.identifier.doi | 10.1007/s00401-011-0896-x | es |
dc.journaltitle | Acta Neuropathologica | es |
dc.publication.volumen | 123 | es |
dc.publication.issue | 1 | es |
dc.publication.initialPage | 53 | es |
dc.publication.endPage | 70 | es |
dc.identifier.sisius | 20035813 | es |
dc.contributor.funder | Instituto de Salud Carlos III | es |
dc.contributor.funder | Junta de Andalucía | es |