Affiliations: [a] Dipartimento di Biologia e Biotecnologie “Lazzaro Spallanzani”, Laboratorio di Biologia Cellulare e Neurobiologia, Università di Pavia, Pavia, Italy | [b] Institut de Neuropatologia, IDIBELL-Hospital Universitari de Bellvitge, Universitat de Barcelona, Hospitalet de Llobregat; CIBERNED (Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas), Catalunya, Spain | [c] Serveis Científico-Tecnics, Unitat de Biología de Bellvitge, Universitat de Barcelona, Hospitalet de Llobregat, Catalunya, Spain
Correspondence:
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Correspondence to: Isidro Ferrer, Institut de Neuropatologia, Servei d'Anatomia Patològica, Hospital Universitari de Bellvitge, carrer Feixa Llarga s/n, 08907 Hospitalet de Llobregat, Spain. Tel.: +34 93 260 7452; Fax: +34 93 260 7503; E-mail: [email protected].
Abstract: Cerebellar amyloid-β (Aβ) deposition in the form of neuritic plaques and Purkinje cell loss are common in certain pedigrees of familial Alzheimer's disease (FAD) mainly linked to PS1 mutations. AβPP/PS1 transgenic mice, here used as a model of FAD, show a few Aβ plaques in the molecular layer of the cerebellum at 6 months, and which increase in number with age. Motor impairment is apparent in transgenic mice aged 12 months. Combined methods have shown degenerated parallel fibers as the main component of dystrophic neurites of Aβ plaques, loss of synaptic contacts between parallel fibers and dendritic spines of Purkinje cells, and degeneration of granule cells starting at 12 months and increasing in mice 18/20 months old. In addition, abnormal mitochondria and focal loss of Purkinje and basket cells, together with occasional axonal torpedoes and increased collaterals of Purkinje cells in mice aged 18/20 months, is suggested to be a concomitant defect presumably related to soluble extracellular or intracellular Aβ. These observations demonstrate serious deterioration of the neuronal circuitry in the cerebellum of AβPP/PS1 transgenic mice, and they provide support for the interpretation of similar alterations occurring in certain pedigrees with FAD.
