Affiliations: [a] Centro de Biología Molecular “Severo Ochoa” CSIC-UAM, Madrid, Spain
| [b] Centro de Investigacion Neurologica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
| [c]
Universidad Autónoma de Madrid (UAM), Madrid, Spain
| [d] Instituto de Tecnologías Biomédicas, Universidad de La Laguna, La Laguna, Spain
Correspondence:
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Correspondence to: Lara Ordoñez-Gutierrez, Centro de Biología Molecular “Severo Ochoa” CSIC-UAM & CIBERNED, Nicolás Cabrera 1, 28049 Madrid, Spain. Tel.: +34 911 964 591; Fax: +34 911 964 420; E-mail: [email protected] and Francisco Wandosell, Centro de Biología Molecular “Severo Ochoa” CSIC-UAM & CIBERNED, Nicolás Cabrera 1, 28049 Madrid, Spain. Tel.: +34 911 964 561; Fax: +34 911 964 420; E-mail: [email protected].
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.
Keywords: AβPP/PS1, AD mouse models, aging, Alzheimer’s disease, amyloid-β, autophagy, cerebellum, glial, sex differences, transgenic mice
