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oai:riuma.uma.es:10630/372122026-03-13T07:38:04Zcom_10630_2254col_10630_37953

Extracellular amyloid-beta and cytotoxic glial activation induce significant entorhinal neuron loss in young PS1(M146L)/APP(751SL) mice. Moreno-González, Inés Baglietto-Vargas, David Sánchez-Varo, Raquel María Jiménez, Sebastián Trujillo-Estrada, Laura Isabel Sánchez-Mejías, Elisabeth Del Rio, Juan Carlos Torres, Manuel Romero-Acebal, Manuel Ruano, Diego Vizuete, María Luisa Vitorica Ferrández, Javier Gutiérrez-Pérez, Antonia Alzheimer, Enfermedad de Neuroglia Sistema nervioso - Degeneración Sistema nervioso - Inflamación https://publishingsupport.iopscience.iop.org/preprint-pre-publication-policy/ Here we demonstrated that extracellular, not intracellular, Aβ and the associated cytotoxic glial neuroinflammatory response are major contributors of early 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 6 months of age. Loss of principal cells occurred selectively in deep layers (primarily layer V) whereas SOM/NPY cell loss was evenly distributed along the cortical column. Neither layer V pyramidal neurons nor SOM/NPY interneurons displayed intracellular Aβ immunoreactivity, even after formic acid retrieval, thus, extracellular factors should be preferentially implicated in this selective neurodegeneration. Amyloid deposits were mainly concentrated in deep layers at 4-6 months, and of relevance was the existence of a potentially cytotoxic inflammatory response (TNFalpha, TRAIL and iNOS mRNAs were upregulated). Moreover, non-plaques associated activated microglial cells and reactive astrocytes expressed TNFalpha and iNOS, respectively. At this age, in the hippocampus of same animals the extracellular Aβ induced a non-cytotoxic glial activation. The opposite glial activation, at the same chronological age, in entorhinal cortex and hippocampus strongly support different mechanisms of disease progression in these two regions highly affected by Aβ pathology. 2025-01-28T17:48:49Z 2025-01-28T17:48:49Z 2009-11-12 journal article 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. https://hdl.handle.net/10630/37212 10.3233/JAD-2009-1192 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional Sage