Through reconstruction of the AD variant-variant PPI network, potential susceptibility genes that interacting with the estrogen receptors ESR1 and ESR2 were identified, including MAPK1, IGF1, AKT1, TP53 and CD44. Additionally, the GPER1 gene was found to interact with the ESR1, ESR2 and EGFR AD susceptibility genes. This evidence concerns the gene GPER1 and Alzheimer disease.