title: Fibroblasts from PS1 mutated pre-symptomatic subjects and Alzheimer's disease patients share a unique protein levels profile.
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.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Magini
authors.forename: Lorena
authors.initials: L
authors.lastname: Urbanelli
authors.forename: Virginia
authors.initials: V
authors.lastname: Ciccarone
authors.forename: Brunella
authors.initials: B
authors.lastname: Tancini
authors.forename: Mario
authors.initials: M
authors.lastname: Polidoro
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Timperio
authors.forename: Lello
authors.initials: L
authors.lastname: Zolla
authors.forename: Andrea
authors.initials: A
authors.lastname: Tedde
authors.forename: Sandro
authors.initials: S
authors.lastname: Sorbi
authors.forename: Carla
authors.initials: C
authors.lastname: Emiliani
mesh_terms: 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
chemical_list: D015415:Biomarkers; C508853:PSEN1 protein, human; D053764:Presenilin-1