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 containing the Arctic mutant Aβ42 gene. We identified 3093 proteins from diseased flies 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 independently of age, are enriched for AD-associated processes and have distinct hub and bottleneck properties in the brain protein interaction network. We also demonstrate widespread ageing-independent brain proteome dysregulation in response to Aβ42, which affects the expression of proteins that are important for brain function and jmay explain the neuronal damage observed in AD.
Footnotes
↵* Joint first authors