Fibroblasts from PS1 Mutated Pre-Symptomatic Subjects and Alzheimer's Disease Patients Share a Unique Protein Levels Profile

• Published in: Journal of Alzheimer's disease Vol. 21; no. 2; pp. 431 - 444
• Main Authors: Magini, Alessandro, Urbanelli, Lorena, Ciccarone, Virginia, Tancini, Brunella, Polidoro, Mario, Timperio, Anna Maria, Zolla, Lello, Tedde, Andrea, Sorbi, Sandro, Emiliani, Carla
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.01.2010
• Subjects: Adult; Alzheimer Disease - diagnosis; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Biomarkers - metabolism; Biopsy; Cells, Cultured; Early Diagnosis; Electrophoresis, Gel, Two-Dimensional; Family Health; Female; Fibroblasts - cytology; Fibroblasts - physiology; Humans; Male; Middle Aged; Presenilin-1 - genetics; Presenilin-1 - metabolism; Proteomics - methods; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; proteome analysis; early markers; Alzheimer's disease; skin fibroblasts
• ISSN: 1387-2877; 1875-8908; 1875-8908
• DOI: 10.3233/JAD-2010-091522

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.