Role of sex hormones in neuroinflammation in Alzheimer's disease

Neuroinflammation, which is mediated by microglia, astrocytes, and infiltrated immune cells and leads to the subsequent production of proinflammatory molecules, is associated with the pathomechanism of Alzheimer's disease (AD). As the incidence of AD is higher in females than males, multiple studies have focused on the relationship between sex hormones and AD pathology. Androgen and estrogen receptors are expressed throughout the brain, including the hippocampus; thus, both sex hormones may regulate brain function, including cognitive function. Endogenous sex hormone levels are depleted by aging and cancer therapies, including prostate cancer and breast cancer therapies. Previous cohort studies have revealed that these conditions may also increase the risk of developing AD. Here we review previous findings from epidemiologic and preclinical studies on AD and provide an overview of the roles of sex hormones as risk factors of AD and regulators of AD pathology, including neuroinflammation. Furthermore, we discuss the therapeutic potential of sex hormone supplementation as a preventive or therapeutic treatment for AD based on the results of randomized control trials.