In addition to the effect of rs405509 on APOE gene expression, the synergistic effect of rs405509 TT and APOE4 was found in AD-related neurodegeneration, which means that the presence of rs40550 may exacerbate the brain changes in high-risk groups such as APOE4 carriers (Choi et al., 2019). This evidence concerns the gene APOE and Alzheimer disease.