Gender, sex steroid hormones, and Alzheimer's disease

This article is part of a Special Issue "Hormones & Neurotrauma". Age-related loss of sex steroid hormones is a established risk factor for the development of Alzheimer's disease (AD) in women and men. While the relationships between the sex steroid hormones and AD are not fully understood, findings from both human and experimental paradigms indicate that depletion of estrogens in women and androgens in men increases vulnerability of the aging brain to AD pathogenesis. We review evidence of a wide range of beneficial neural actions of sex steroid hormones that may contribute to their hypothesized protective roles against AD. Both estrogens and androgens exert general neuroprotective actions relevant to a several neurodegenerative conditions, some in a sex-specific manner, including protection from neuron death and promotion of select aspects of neural plasticity. In addition, estrogens and androgens regulate key processes implicated in AD pathogenesis, in particular the accumulation of β-amyloid protein. We discuss evidence of hormone-specific mechanisms related to the regulation of the production and clearance of β-amyloid as critical protective pathways. Continued elucidation of these pathways promises to yield effective hormone-based strategies to delay development of AD. ► Age-related estrogen depletion in women is a risk factor for Alzheimer's disease. ► Age-related androgen depletion in men is a risk factor for Alzheimer's disease. ► Relationships between hormones and Alzheimer's are often sex-specific. ► Estrogens and androgens reduce β-amyloid protein to reduce Alzheimer risk.