Alzheimer’s disease (AD) remains the most common form of dementia, affecting 50 million people worldwide. Recent studies from our laboratory have established that perturbations of the gut microbiome with antibiotics lead to an attenuation of amyloid beta deposition and alterations in the physiology of microglia, cells that are critical for amyloid beta clearance. Importantly, these findings are unique to male but not female mice. Genetic and epidemiological studies have documented that women are at higher risk for AD than men. Is estrogen an important hormone that drives these differences? The current proposal seeks to delineate the mechanism(s) by which circulating levels of estrogen influence amyloid beta deposition and neuroinflammation. Our investigations will provide important information pertaining to the role of female sex hormones in modulating pathogenesis in our mouse models—findings that we anticipate will offer new therapeutic targets that will alter the onset and/or progression of AD in women.