title: A unique gene expression signature discriminates familial Alzheimer's disease mutation carriers from their wild-type siblings.
abstract: Alzheimer's disease (AD) is a neurodegenerative disease with an insidious onset and progressive course that inevitably leads to death. The current diagnostic tools do not allow for diagnosis until the disease has lead to irreversible brain damage. Genetic studies of autosomal dominant early onset familial AD has identified three causative genes: amyloid precursor protein (APP), presenilin 1 and 2 (PSEN1 and PSEN2). We performed a global gene expression analysis on fibroblasts from 33 individuals (both healthy and demented mutation carriers as well as wild-type siblings) from three families segregating the APP(SWE), APP(ARC) and PSEN1 H163Y mutations, respectively. The mutations cause hereditary progressive cognitive disorder, including typical autosomal dominant AD. Our data show that the mutation carriers share a common gene expression profile significantly different from that of their wild-type siblings. The results indicate that the disease process starts several decades before the onset of cognitive decline, suggesting that presymptomatic diagnosis of AD and other progressive cognitive disorders may be feasible in the near future.
authors.affiliation: Research Division, Sumitomo Pharmaceuticals Co., Ltd., 3-1-98 Kasugade-naka, Konohana, Osaka 554-0022, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Nagasaka
authors.forename: Karin
authors.initials: K
authors.lastname: Dillner
authors.forename: Hayao
authors.initials: H
authors.lastname: Ebise
authors.forename: Reiji
authors.initials: R
authors.lastname: Teramoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Lena
authors.initials: L
authors.lastname: Lilius
authors.forename: Karin
authors.initials: K
authors.lastname: Axelman
authors.forename: Charlotte
authors.initials: C
authors.lastname: Forsell
authors.forename: Akira
authors.initials: A
authors.lastname: Ito
authors.forename: Bengt
authors.initials: B
authors.lastname: Winblad
authors.forename: Toru
authors.initials: T
authors.lastname: Kimura
authors.forename: Caroline
authors.initials: C
authors.lastname: Graff
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D016000:Cluster Analysis; D005347:Fibroblasts / Q000378:metabolism; D020869:Gene Expression Profiling; D005799:Genes, Dominant / Q000235:genetics; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D046228:Microarray Analysis; D009154:Mutation / Q000235:genetics*; D053764:Presenilin-1; D025341:Principal Component Analysis
chemical_list: D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1