An integrative systems-biology approach defines mechanisms of Alzheimer's disease neurodegeneration.

ABSTRACT: Despite years of intense investigation, the mechanisms underlying neuronal death in Alzheimer's disease, the most common neurodegenerative disorder, remain incompletely understood. To define relevant pathways, we integrated the results of an unbiased, genome-scale forward genetic screen for age-associated neurodegeneration in Drosophila with human and Drosophila Alzheimer's disease-associated multi-omics. We measured proteomics, phosphoproteomics, and metabolomics in Drosophila models of Alzheimer's disease and identified Alzheimer's disease human genetic variants that modify expression in disease-vulnerable neurons. We used a network optimization approach to integrate these data with previously published Alzheimer's disease multi-omic data. We computationally predicte

SUBMITTER: Leventhal MJ 

PROVIDER: S-EPMC10980014 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature