FIBROBLASTS FROM PS1 MUTATED PRE-SYMPTOMATIC SUBJECTS AND ALZHEIMER’S DISEASE PATIENTS SHARE A UNIQUE PROTEIN LEVELS PROFILE.

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 presymptomatic subjects, using a 2DPAGE based approach and then identifying proteins by mass spectrometry. We compared primary fibroblast cultures from skin biopsy of presenilin 1 (PS1) mutated patients, presymptomatic subjects carrying mutations in the PS1 gene but healthy at the time of skin biopsy, and agematched 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 ubiquitinproteasome 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.