Affiliations: [a] Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy | [b] Department of Environmental Sciences, University of Tuscia, Viterbo, Italy | [c] Department of Neurological Sciences and Psychiatry, University of Firenze, Firenze, Italy
Correspondence:
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Correspondence to: Prof. Carla Emiliani, University of Perugia, Department of Experimental Medicine and Biochemical Sciences, Via del Giochetto, 06123 Perugia, Italy. Tel./Fax: +39 0755857436; E-mail: emiliani@unipg.it.
Abstract: In Alzheimer's disease (AD), a major goal is to improve early detection, as the diagnosis cannot be made until patients exhibit a noticeable decline in cognition and the brain is irreversibly damaged. With this aim in mind, we performed proteome analysis of familial AD fibroblasts from both demented and pre-symptomatic subjects, using a 2D-PAGE based approach and then identifying proteins by mass spectrometry. We compared primary fibroblast cultures from skin biopsy of presenilin 1 (PS1) mutated patients, pre-symptomatic subjects carrying mutations in the PS1 gene but healthy at the time of skin biopsy, and age-matched individuals as control. 15 differentially expressed proteins were identified in PS1 mutated fibroblasts, related to cell adhesion and cytoskeleton, energy and glucose metabolism, stress response and ubiquitin-proteasome system, and signal transduction. Interestingly, many of these proteins have been previously associated with AD and neurodegeneration. Overall results indicated that a unique protein profile can be identified by peripheral cell analysis of PS1 mutated individuals, and showed that fibroblasts are a useful cell model for pathological investigations as well as identification of potential biomarkers for AD diagnosis at early stages.
Keywords: Alzheimer's disease, early markers, proteome analysis, skin fibroblasts
