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

Published version
Peer-reviewed

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Type

Article

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Authors

Bean, DM 
Bilsland, E 
Boyer, H 
Fischer, BE 

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.

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Keywords

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

Journal Title

Sci Rep

Conference Name

Journal ISSN

2045-2322
2045-2322

Volume Title

3

Publisher

Springer Science and Business Media LLC
Sponsorship
Wellcome Trust (089703/Z/09/Z)
Medical Research Council (G0700990)
Medical Research Council (MC_G1000734)
Alzheimer's Research UK (ARUK-ESG2013-7)