Abnormal accumulation of autophagic vesicles correlates with axonal and synaptic pathology in young Alzheimer’s mice hippocampus
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Abnormal accumulation of autophagic vesicles correlates with axonal and synaptic pathology in young Alzheimer’s mice hippocampus

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Abnormal accumulation of autophagic vesicles correlates with axonal and synaptic pathology in young Alzheimer’s mice hippocampus

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dc.contributor.author Sanchez-Varo, Raquel es_ES
dc.contributor.author Trujillo-Estrada, Laura es_ES
dc.contributor.author Sanchez-Mejias, Elisabeth es_ES
dc.contributor.author Torres, Manuel es_ES
dc.contributor.author Baglietto-Vargas, David es_ES
dc.contributor.author Moreno-Gonzalez, Ines es_ES
dc.contributor.author De Castro, Vanessa es_ES
dc.contributor.author Jimenez, Sebastian es_ES
dc.contributor.author Ruano, Diego es_ES
dc.contributor.author Vizuete, Marisa es_ES
dc.contributor.author Davila, Jose Carlos es_ES
dc.contributor.author García Verdugo, José Manuel es_ES
dc.contributor.author Jimenez, Antonio Jesus es_ES
dc.contributor.author Vitorica, Javier es_ES
dc.contributor.author Gutierrez, Antonia es_ES
dc.date.accessioned 2015-06-22T09:52:41Z
dc.date.available 2015-06-22T09:52:41Z
dc.date.issued 2012 es_ES
dc.identifier.uri http://hdl.handle.net/10550/44683
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 Aβ oligomers were identified, the presence of A11-immunopositive Aβ plaques also suggested a direct role of plaque-associated Aβ 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_ES
dc.source Acta Neuropathologica Vol. 123 Issue 1: pp. 53-70 es_ES
dc.subject PS1/APP transgenic mice es_ES
dc.subject Dystrophic neurites es_ES
dc.subject Electron microscopy es_ES
dc.subject LC3 es_ES
dc.subject Amyloid plaques es_ES
dc.subject Presynaptic terminals es_ES
dc.title Abnormal accumulation of autophagic vesicles correlates with axonal and synaptic pathology in young Alzheimer’s mice hippocampus es_ES
dc.type info:eu-repo/semantics/article es_ES
dc.identifier.doi 10.1007/s00401-011-0896-x es_ES
dc.identifier.idgrec 076893 es_ES

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