MAPT and Alzheimer disease: For instance, in chimeric human cerebral organoids (chCOs), astrocytes and neurons carrying the APOE4 genotype could jointly promote tau phosphorylation in neurons, closely linked to the role of APOE4 in increasing cholesterol levels and lipid droplet content, suggesting that APOE4 may affect tau phosphorylation in AD by influencing lipid metabolism.279 Litvinchuk et al. revealed a potential synergistic effect between APOE4 and tau pathology, wherein APOE4 may induce the abnormal accumulation of certain cholesterol esters in glial cells.