Through the reconstruction of the AD variant-variant PPI network, comprising genetic susceptibility genes associated with AD, we have identified potential susceptibility genes that interact with ESR1, ESR2 and GPER1. ESR1 and ESR2 genes are the primary receptors targeted by hormone replacement drugs in menopause, while, GPER1, also expressed in the brain, may modulate rapid estrogen processes like calcium fluxes (32). The gene discussed is GPER1; the disease is Alzheimer disease.