title: Role of genes linked to sporadic Alzheimer's disease risk in the production of β-amyloid peptides.
abstract: Alzheimer's disease (AD) is characterized by the presence of toxic protein aggregates or plaques composed of the amyloid β (Aβ) peptide. Various lengths of Aβ peptide are generated by proteolytic cleavages of the amyloid precursor protein (APP). Mutations in many familial AD-associated genes affect the production of the longer Aβ42 variant that preferentially accumulates in plaques. In the case of sporadic or late-onset AD, which accounts for greater than 95% of cases, several genes are implicated in increasing the risk, but whether they also cause the disease by altering amyloid levels is currently unknown. Through loss of function studies in a model cell line, here RNAi-mediated silencing of several late onset AD genes affected Aβ levels is shown. However, unlike the genes underlying familial AD, late onset AD-susceptibility genes do not specifically alter the Aβ42/40 ratios and suggest that these genes probably contribute to AD through distinct mechanisms.
authors.affiliation: Systems and Cell Biology of Neurodegeneration, Division of Psychiatry Research, University of Zurich, 8008 Zurich, Switzerland.
authors.forename: Jitin
authors.initials: J
authors.lastname: Bali
authors.forename: Ali Hashemi
authors.initials: AH
authors.lastname: Gheinani
authors.forename: Sebastian
authors.initials: S
authors.lastname: Zurbriggen
authors.forename: Lawrence
authors.initials: L
authors.lastname: Rajendran
mesh_terms: D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000235:genetics; D049109:Cell Proliferation; D015891:Cystatins / Q000235:genetics; D004843:Epistasis, Genetic; D020868:Gene Silencing; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006367:HeLa Cells; D006801:Humans; D008957:Models, Genetic; D009154:Mutation; D010446:Peptide Fragments / Q000235:genetics*; D058225:Plaque, Amyloid / Q000378:metabolism; D034622:RNA Interference; D012306:Risk
chemical_list: D016229:Amyloid beta-Peptides; D015891:Cystatins; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)