Androgen regulation of beta-amyloid protein and the risk of Alzheimer's disease

Advancing age is the most significant risk factor for the development of Alzheimer's disease (AD), however the age-related changes that underlie this effect remain unclear. In men, one normal consequence of aging is a robust decline in circulating and brain levels of the sex steroid hormone testosterone. Testosterone depletion leads to functional impairments and increased risk of disease in androgen-responsive tissues throughout the body, including brain. In this review we discuss the relationship between age-related testosterone depletion and the development of AD. Specifically, we focus on androgen regulation of P-amyloid protein (A beta), the accumulation of which is a key initiating factor in AD pathogenesis. Emerging data suggest that the regulatory actions of androgens on both A beta and the development of AD support consideration of androgen therapy for the prevention and treatment of AD. (c) 2007 Elsevier B.V. All rights reserved.