Dynamic changes in the brain protein interaction network correlates with progression of Aβ42 pathology in Drosophila

Scholes, Harry M.; Cryar, Adam; Kerr, Fiona; Sutherland, David; Gethings, Lee A.; Vissers, Johannes P. C.; Lees, Jonathan G.; Orengo, Christine A.; Partridge, Linda; Thalassinos, Konstantinos

Abstract

Alzheimer’s disease (AD), the most prevalent form of dementia, is a progressive and devastating neurodegenerative condition for which there are no effective treatments. Understanding the molecular pathology of AD during disease progression may identify new ways to reduce neuronal damage. Here, we present a longitudinal study tracking dynamic proteomic alterations in the brains of an inducible Drosophila melanogaster model of AD expressing the Arctic mutant Aβ42 gene. We identified 3093 proteins from flies that were induced to express Aβ42 and age-matched healthy controls using label-free quantitative ion-mobility data independent analysis mass spectrometry. Of these, 228 proteins were significantly altered by Aβ42 accumulation and were enriched for AD-associated processes. Network analyses further revealed that these proteins have distinct hub and bottleneck properties in the brain protein interaction network, suggesting that several may have significant effects on brain function. Our unbiased analysis provides useful insights into the key processes governing the progression of amyloid toxicity and forms a basis for further functional analyses in model organisms and translation to mammalian systems.

Citation

Scholes, H. M., Cryar, A., Kerr, F., Sutherland, D., Gethings, L. A., Vissers, J. P. C., …Thalassinos, K. (2020). Dynamic changes in the brain protein interaction network correlates with progression of Aβ42 pathology in Drosophila. Scientific Reports, 10(1), Article 18517 (2020). https://doi.org/10.1038/s41598-020-74748-9

• Journal Article Type: Article
• Acceptance Date: Aug 18, 2020
• Online Publication Date: Oct 28, 2020
• Publication Date: 2020-12
• Deposit Date: Apr 14, 2021
• Publicly Available Date: Apr 14, 2021
• Journal: Scientific Reports
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 10
• Issue: 1
• Article Number: 18517 (2020)
• DOI: https://doi.org/10.1038/s41598-020-74748-9
• Keywords: Mass spectrometry, Protein–protein interaction networks, Proteomics
• Public URL: http://researchrepository.napier.ac.uk/Output/2761367