title: AβPP/PS1 Transgenic Mice Show Sex Differences in the Cerebellum Associated with Aging.
abstract: Cerebellar pathology has been related to presenilin 1 mutations in certain pedigrees of familial Alzheimer's disease. However, cerebellum tissue has not been intensively analyzed in transgenic models of mutant presenilins. Furthermore, the effect of the sex of the mice was not systematically analyzed, despite the fact that important gender differences in the evolution of the disease in the human population have been described. We analyzed whether the progression of amyloidosis in a double transgenic mouse, AβPP/PS1, is susceptible to aging and differentially affects males and females. The accumulation of amyloid in the cerebellum differentially affects males and females of the AβPP/PS1 transgenic line, which was found to be ten-fold higher in 15-month-old females. Amyloid-β accumulation was more evident in the molecular layer of the cerebellum, but glia reaction was only observed in the granular layer of the older mice. The sex divergence was also observed in other neuronal, survival, and autophagic markers. The cerebellum plays an important role in the evolution of the pathology in this transgenic mouse model. Sex differences could be crucial for a complete understanding of this disease. We propose that the human population could be studied in this way. Sex-specific treatment strategies in human populations could show a differential response to the therapeutic approach.
authors: Centro de Biología Molecular "Severo Ochoa" CSIC-UAM, Madrid, Spain.|Centro de Investigacion Neurologica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors: Lara
authors: L
authors: Ordoñez-Gutierrez
authors: Universidad Autónoma de Madrid (UAM), Madrid, Spain.
authors: Ivan
authors: I
authors: Fernandez-Perez
authors: Instituto de Tecnologías Biomédicas, Universidad de La Laguna, La Laguna, Spain.
authors: Jose Luis
authors: JL
authors: Herrera
authors: Centro de Investigacion Neurologica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors: Marta
authors: M
authors: Anton
authors: Centro de Biología Molecular "Severo Ochoa" CSIC-UAM, Madrid, Spain.
authors: Irene
authors: I
authors: Benito-Cuesta
authors: Centro de Biología Molecular "Severo Ochoa" CSIC-UAM, Madrid, Spain.|Centro de Investigacion Neurologica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors: Francisco
authors: F
authors: Wandosell
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D053764:Presenilin-1 / Q000235:genetics; D012727:Sex Characteristics
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D053764:Presenilin-1; C078592:amyloid beta-protein (1-40)
keywords: AD mouse models; Alzheimer’s disease; AβPP/PS1; aging; amyloid-β; autophagy; cerebellum; glial; sex differences; transgenic mice