This ERα/IGF-1Rβ tandem has been shown to be cross-talked modulated by their natural ligands, E2 and IGF-1, which mutually cooperate in the prevention of age-related neuronal dysfunction (Alonso and Gonzalez, 2012; Arevalo et al., 2015), and are crucial in brain preservation against AD (Marin, 2011; Lan et al., 2015). This evidence concerns the gene ESR1 and Alzheimer disease.