APOE genotype‐dependent effects of enhanced BMP signaling on astrocytes and co‐cultured neurons

Increased BMP signaling alters the physiology of astrocytes in an APOE-dependent manner, with E4 astrocytes exhibiting more abnormalities in lipid metabolism than E3 astrocytes. Specifically, BMP-treated E4 astrocytes have greater lipid droplet accumulation due to increased lipid generation, reduced lipid breakdown, and lack of beta oxidation when compared to E3 astrocytes treated with BMP4. E4 astrocytes exert greater effects than E3 astrocytes on the disease phenotype of co-cultured AD neurons, with increases in phosphorylated tau and decreases in oxidative phosphorylation efficiency. This suggests that enhanced BMP4 signaling in the aging brain may be one of the contributing factors to development of AD.