RT Journal Article
T1 Extracellular amyloid-beta and cytotoxic glial activation induce significant entorhinal neuron loss in young PS1(M146L)/APP(751SL) mice.
A1 Moreno-González, Inés
A1 Baglietto-Vargas, David
A1 Sánchez-Varo, Raquel María
A1 Jiménez, Sebastián
A1 Trujillo-Estrada, Laura Isabel
A1 Sánchez-Mejías, Elisabeth
A1 Del Rio, Juan Carlos
A1 Torres, Manuel
A1 Romero-Acebal, Manuel
A1 Ruano, Diego
A1 Vizuete, María Luisa
A1 Vitorica Ferrández, Javier
A1 Gutiérrez-Pérez, Antonia
K1 Alzheimer, Enfermedad de
K1 Neuroglia
K1 Sistema nervioso - Degeneración
K1 Sistema nervioso  - Inflamación
AB Here we demonstrated that extracellular, not intracellular, Aβ and theassociated cytotoxic glial neuroinflammatory response are major contributors ofearly neuronal loss in a PS1xAPP model. A significant loss of principal (27%)and SOM/NPY (56-46%) neurons was found in the entorhinal cortex at 6months of age. Loss of principal cells occurred selectively in deep layers(primarily layer V) whereas SOM/NPY cell loss was evenly distributed along thecortical column. Neither layer V pyramidal neurons nor SOM/NPY interneuronsdisplayed intracellular Aβ immunoreactivity, even after formic acid retrieval,thus, extracellular factors should be preferentially implicated in this selectiveneurodegeneration. Amyloid deposits were mainly concentrated in deep layersat 4-6 months, and of relevance was the existence of a potentially cytotoxicinflammatory response (TNFalpha, TRAIL and iNOS mRNAs wereupregulated). Moreover, non-plaques associated activated microglial cells andreactive astrocytes expressed TNFalpha and iNOS, respectively. At this age, inthe hippocampus of same animals the extracellular Aβ induced a non-cytotoxicglial activation. The opposite glial activation, at the same chronological age, inentorhinal cortex and hippocampus strongly support different mechanisms ofdisease progression in these two regions highly affected by Aβ pathology.
PB Sage
YR 2009
FD 2009-11-12
LK https://hdl.handle.net/10630/37212
UL https://hdl.handle.net/10630/37212
LA eng
NO Moreno-Gonzalez I, Baglietto-Vargas D, Sanchez-Varo R, Jimenez S, Trujillo-Estrada L, Sanchez-Mejias E, Del Rio JC, Torres M, Romero-Acebal M, Ruano D, Vizuete M, Vitorica J, Gutierrez A. Extracellular amyloid-beta and cytotoxic glial activation induce significant entorhinal neuron loss in young PS1(M146L)/APP(751SL) mice. J Alzheimers Dis. 2009;18(4):755-76. doi: 10.3233/JAD-2009-1192. PMID: 19661615.
NO https://publishingsupport.iopscience.iop.org/preprint-pre-publication-policy/
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026