Identification of novel modifiers of Aβ toxicity by transcriptomic analysis in the fruitfly

G Favrin; D M Bean; E Bilsland; H Boyer; B E Fischer; S Russell; D C Crowther; H A Baylis; S G Oliver; M E Giannakou

doi:10.1038/srep03512

Identification of novel modifiers of Aβ toxicity by transcriptomic analysis in the fruitfly

Sci Rep. 2013 Dec 16:3:3512. doi: 10.1038/srep03512.

Authors

G Favrin¹, D M Bean¹, E Bilsland², H Boyer³, B E Fischer⁴, S Russell⁴, D C Crowther⁵, H A Baylis³, S G Oliver², M E Giannakou³

Affiliations

¹ 1] Cambridge Systems Biology Centre, University of Cambridge, Cambridge, CB2 1GA, UK [2] Department of Biochemistry, University of Cambridge, Cambridge, CB2 1GA, UK [3].
² 1] Cambridge Systems Biology Centre, University of Cambridge, Cambridge, CB2 1GA, UK [2] Department of Biochemistry, University of Cambridge, Cambridge, CB2 1GA, UK.
³ Department of Zoology, University of Cambridge, Cambridge, CB2 3EJ, UK.
⁴ 1] Cambridge Systems Biology Centre, University of Cambridge, Cambridge, CB2 1GA, UK [2] Department of Genetics, University of Cambridge, Cambridge, CB2 3EH, UK.
⁵ Department of Genetics, University of Cambridge, Cambridge, CB2 3EH, UK.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aging
Amyloid beta-Peptides / toxicity*
Animals
Cluster Analysis
Computational Biology
Drosophila / drug effects*
Drosophila / genetics*
Female
Gene Expression Profiling*
Gene Expression Regulation / drug effects*
Immunity, Innate / genetics
Male
Molecular Chaperones / genetics
Oxidative Stress / genetics
Phenotype
RNA Interference
Transcriptome*

Substances

Amyloid beta-Peptides
Molecular Chaperones

Abstract

Publication types

MeSH terms

Substances

Grants and funding