Figure 3.

APOE, ABCA1, and inflammation. (A) Neuronal NMDA stimulation increased fatty acid and triglycerides (TGs) leading to decreased mitochondrial respiration, lipid peroxidation, and increased reactive oxygen species (ROS); in turn leading to lipotoxicity and neuronal death. Transport of fatty acids, TGs and lipid peroxidation products (LPPs) from neurons to astrocytes by lipidated APOE rescued neurons by lysosomal catabolism of fatty acids, storage in lipid droplets, and use for mitochondrial oxidative phosphorylation; which was accompanied by transcriptional upregulation of LXR and NRF2 target genes. (B) APOE4 neurons showed 36% lower APOE, reduced neurite branching, elevated fatty acids and TGs, and decreased mitochondrial function and glucose metabolism. APOE4 astrocytes were less efficient at transporting lipids and fatty acids from neurons and at fatty acid catabolism and energy conversion, containing fragmented mitochondria and elevated TGs.