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.
|
Authors | Alessandro Magini, Lorena Urbanelli, Virginia Ciccarone, Brunella Tancini, Mario Polidoro, Anna Maria Timperio, Lello Zolla, Andrea Tedde, Sandro Sorbi, Carla Emiliani |
Journal | Journal of Alzheimer's disease : JAD
(J Alzheimers Dis)
Vol. 21
Issue 2
Pg. 431-44
( 2010)
ISSN: 1875-8908 [Electronic] Netherlands |
PMID | 20555143
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Biomarkers
- PSEN1 protein, human
- Presenilin-1
|
Topics |
- Adult
- Alzheimer Disease
(diagnosis, genetics, metabolism)
- Biomarkers
(metabolism)
- Biopsy
- Cells, Cultured
- Early Diagnosis
- Electrophoresis, Gel, Two-Dimensional
- Family Health
- Female
- Fibroblasts
(cytology, physiology)
- Humans
- Male
- Middle Aged
- Presenilin-1
(genetics, metabolism)
- Proteomics
(methods)
- Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
|