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 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.
Magini
Alessandro
A
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
Urbanelli
Lorena
L
Ciccarone
Virginia
V
Tancini
Brunella
B
Polidoro
Mario
M
Timperio
Anna Maria
AM
Zolla
Lello
L
Tedde
Andrea
A
Sorbi
Sandro
S
Emiliani
Carla
C
D000328:Adult; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D002478:Cells, Cultured; D042241:Early Diagnosis; D015180:Electrophoresis, Gel, Two-Dimensional; D005192:Family Health; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D053764:Presenilin-1 / Q000235:genetics* / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D015415:Biomarkers; C508853:PSEN1 protein, human; D053764:Presenilin-1