Interactions between inflammation, sex steroids, and Alzheimer's disease risk factors

Alzheimer's disease (AD) is an age-related neurodegenerative disorder for which there are no effective strategies to prevent or slow its progression. Because AD is multifactorial, recent research has focused on understanding interactions among the numerous risk factors and mechanisms underlying the disease. One mechanism through which several risk factors may be acting is inflammation. AD is characterized by chronic inflammation that is observed before clinical onset of dementia. Several genetic and environmental risk factors for AD increase inflammation, including apolipoprotein E4, obesity, and air pollution. Additionally, sex steroid hormones appear to contribute to AD risk, with age-related losses of estrogens in women and androgens in men associated with increased risk. Importantly, sex steroid hormones have anti-inflammatory actions and can interact with several other AD risk factors. This review examines the individual and interactive roles of inflammation and sex steroid hormones in AD, as well as their relationships with the AD risk factors apolipoprotein E4, obesity, and air pollution.