title: Identification of novel modifiers of Aβ toxicity by transcriptomic analysis in the fruitfly.
abstract: The strongest risk factor for developing Alzheimer's Disease (AD) is age. Here, we study the relationship between ageing and AD using a systems biology approach that employs a Drosophila (fruitfly) model of AD in which the flies overexpress the human Aβ42 peptide. We identified 712 genes that are differentially expressed between control and Aβ-expressing flies. We further divided these genes according to how they change over the animal's lifetime and discovered that the AD-related gene expression signature is age-independent. We have identified a number of differentially expressed pathways that are likely to play an important role in the disease, including oxidative stress and innate immunity. In particular, we uncovered two new modifiers of the Aβ phenotype, namely Sod3 and PGRP-SC1b.
authors: 1] Cambridge Systems Biology Centre, University of Cambridge, Cambridge, CB2 1GA, UK [2] Department of Biochemistry, University of Cambridge, Cambridge, CB2 1GA, UK [3].
authors: G
authors: G
authors: Favrin
authors: 1] Cambridge Systems Biology Centre, University of Cambridge, Cambridge, CB2 1GA, UK [2] Department of Biochemistry, University of Cambridge, Cambridge, CB2 1GA, UK [3].
authors: D M
authors: DM
authors: Bean
authors: 1] Cambridge Systems Biology Centre, University of Cambridge, Cambridge, CB2 1GA, UK [2] Department of Biochemistry, University of Cambridge, Cambridge, CB2 1GA, UK.
authors: E
authors: E
authors: Bilsland
authors: Department of Zoology, University of Cambridge, Cambridge, CB2 3EJ, UK.
authors: H
authors: H
authors: Boyer
authors: 1] Cambridge Systems Biology Centre, University of Cambridge, Cambridge, CB2 1GA, UK [2] Department of Genetics, University of Cambridge, Cambridge, CB2 3EH, UK.
authors: B E
authors: BE
authors: Fischer
authors: 1] Cambridge Systems Biology Centre, University of Cambridge, Cambridge, CB2 1GA, UK [2] Department of Genetics, University of Cambridge, Cambridge, CB2 3EH, UK.
authors: S
authors: S
authors: Russell
authors: Department of Genetics, University of Cambridge, Cambridge, CB2 3EH, UK.
authors: D C
authors: DC
authors: Crowther
authors: Department of Zoology, University of Cambridge, Cambridge, CB2 3EJ, UK.
authors: H A
authors: HA
authors: Baylis
authors: 1] Cambridge Systems Biology Centre, University of Cambridge, Cambridge, CB2 1GA, UK [2] Department of Biochemistry, University of Cambridge, Cambridge, CB2 1GA, UK.
authors: S G
authors: SG
authors: Oliver
authors: Department of Zoology, University of Cambridge, Cambridge, CB2 3EJ, UK.
authors: M E
authors: ME
authors: Giannakou
mesh_terms: D000375:Aging; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D016000:Cluster Analysis; D019295:Computational Biology; D004330:Drosophila / Q000187:drug effects* / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D007113:Immunity, Innate / Q000235:genetics; D008297:Male; D018832:Molecular Chaperones / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics; D010641:Phenotype; D034622:RNA Interference; D059467:Transcriptome
chemical_list: D016229:Amyloid beta-Peptides; D018832:Molecular Chaperones