Neuronal ROS-induced glial lipid droplet formation is altered by loss of Alzheimer’s disease–associated genes

Significance Multiple studies have implicated dozens of risk loci that may be associated with Alzheimer’s disease (AD), but common mechanisms underlying how they may contribute to disease onset or progression remain elusive. This study identifies cell-specific roles for Drosophila orthologs of AD risk genes in lipid droplet formation that, when disrupted, lead to neurodegeneration. Our work reinforces a critical role for the sequestration of peroxidated lipids in glia, and places Apolipoprotein E ε4 (APOE4) with other AD risk factors in the transfer process of lipids from neurons to glia to form lipid droplets.