Figure 1.

Overview of analytical framework in this study for multi-omic integration to understand the biological processes underlying neurodegeneration. We performed a forward genetic screen for age-associated neurodegeneration in Drosophila. We measured proteomics, phosphoproteomics and metabolomics in amyloid β (gold) and tau (purple) models of Alzheimer’s disease and performed an eQTL meta-analysis of previous Alzheimer’s disease studies. We used a network integration model to integrate these new data with previously published human proteomics, human genetics, human lipidomics, and Drosophila modifiers of tau-mediated neurotoxicity. We tested hypotheses generated from this network model in Drosophila and human iPSC-derived neural progenitor cells. Icons created with Biorender.com.