This network was generated as part of the manuscript A systems-biology approach connects aging mechanisms with Alzheimer’s disease pathogenesis, Leventhal et al.
A link to the manuscript will be provided when uploaded to a preprint server
Edges are annotated by their degree of confidence in the "weight" column. Nodes can be shaded by their effect size ("magnitude"), importance in the network ("prize"), robustness to edge permutations ("robustness") and how sensitive they are to permutation of the node weights ("specificity"). Nodes can also be grouped according to their membership in subnetworks identified by Louvain clustering ("louvain clusters"). These clusters are annotated by the biological process enriched in these clusters. The shape of the nodes can be changed according to their data type of origin ("general_datatype"). For a more specific description, shape the nodes by "data_source"
Age is the strongest risk factor for developing Alzheimer’s disease, the most common neurodegenerative disorder. However, the mechanisms connecting advancing age to neurodegeneration in Alzheimer’s disease are incompletely understood. We conducted an unbiased, genome-scale, forward genetic screen for age-associated neurodegeneration in Drosophila to identify the underlying biological processes required for maintenance of aging neurons. To connect genetic screen hits to Alzheimer’s disease pathways, we measured proteomics, phosphoproteomics, and metabolomics in Drosophila models of Alzheimer’s disease. We further identified Alzheimer’s disease human genetic variants that modify expression in disease- vulnerable neurons. Through multi-omic, multi-species network integration of these data, we identified relationships between screen hits and tau-mediated neurotoxicity. Furthermore, we computationally and experimentally identified relationships between screen hits and DNA damage in Drosophila and human iPSC-derived neural progenitor cells. Our work identifies candidate pathways that could be targeted to attenuate the effects of age on neurodegeneration and Alzheimer’s disease.