ESR1 and Alzheimer disease: Based on the overall findings, we, therefore, propose that the ESR1 variant identified in our study might act by perturbing the subtlety of cholesterol content in brain, to promote Aβ production as well as increase Aβ toxicity, and consequently induce cognitive decline which is manifested by worsening cognitive symptoms slightly in the elderly with MCI and severely in AD seniors, whereby participating in the pathological process of AD.