RT Journal Article
T1 Abnormal accumulation of autophagic vesicles correlates with axonal and synaptic pathology in young Alzheimer’s mice hippocampus.
A1 Sánchez-Varo, Raquel María
A1 Trujillo-Estrada, Laura Isabel
A1 Sánchez-Mejías, Elisabeth
A1 Torres, Manuel
A1 Baglietto-Vargas, David
A1 Moreno-González, Inés
A1 De Castro, Vanessa
A1 Jiménez, Sebastián
A1 Ruano, Diego
A1 Vizuete, Marisa
A1 Dávila-Cansino, José Carlos
A1 García-Verdugo, José Manuel
A1 Jiménez-Lara, Antonio Jesús
A1 Vitorica Ferrández, Javier
A1 Gutiérrez-Pérez, Antonia
K1 Alzheimer, Enfermedad de - Modelos animales
K1 Desarrollo neurológico
K1 Hipocampo (Cerebro)
AB Dystrophic neurites associated with amyloid plaques precede neuronal death and manifest early inAlzheimer’s disease (AD). In this work we have characterized the plaque-associated neuritic pathology in thehippocampus 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 amyloid-beta oligomers were identified, the presence of A11-immunopositive amyloid plaques also suggested a direct role of plaque-associated amyloid-beta 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.
PB Springer Nature
YR 2012
FD 2012
LK https://hdl.handle.net/10630/31856
UL https://hdl.handle.net/10630/31856
LA eng
NO Sanchez-Varo R, Trujillo-Estrada L, Sanchez-Mejias E, Torres M, Baglietto-Vargas D, Moreno-Gonzalez I, De Castro V, Jimenez S, Ruano D, Vizuete M, Davila JC, Garcia-Verdugo JM, Jimenez AJ, Vitorica J, Gutierrez A. Abnormal accumulation of autophagic vesicles correlates with axonal and synaptic pathology in young Alzheimer's mice hippocampus. Acta Neuropathol. 2012 Jan;123(1):53-70. doi: 10.1007/s00401-011-0896-x. Epub 2011 Oct 22. PMID: 22020633; PMCID: PMC3249205.
NO Fondo de Investigación Sanitaria (FIS)-Instituto de Salud Carlos III de España. Ref. PS09/00099 (A.G.), ref. PS09/00151 (J.V.), ref. PS09/00848 (D.R.) y ref. PS09/00376 (A.J.J.)Proyectos de la Junta de Andalucía SAS P09/496 (A.G.) y CTS-4795 (J.V.).R.S.V., V.D.C. y S.J. contratados CIBERNED. E.S.M. y L.T.E. becas predoctorales del programa FPU.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 21 ene 2026