Mitochondrial-associated membranes (MAMs) is a special domain for communication and material exchange between mitochondrial outer membrane and endoplasmic reticulum membrane, which performs various biological processes of cell life activities under different conditions. MAMs dysfunction-mediated calcium homeostasis imbalance, endoplasmic reticulum stress, mitophagy defects, mitochondrial fission/fusion dynamics imbalance, lipid metabolism disorders, and inflammatory responses are the key pathogenesis of Alzheimer’s disease (AD). This article reviews the structure and function of MAMs, their involvement in AD pathology and drug intervention targets, and discusses the role of MAMs in the pathogenesis of AD and the latest mechanism research progress, in order to provide new ideas for the prevention and treatment of AD.