APP and Alzheimer disease: Consistent with our findings, a recent study reported C3aR-dependent activation of HIF1α signaling in microglia and described a C3aR-dependent reduction in mitochondrial respiration and elevated lipid species in microglia of APP-KI AD model mice, although this was demonstrated using global deletion of C3aR, which is expressed by vascular endothelial cells in addition to microglia [48], so it is currently unclear whether these effects are direct or indirect.