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As aging is associated with decreased estradiol production in women, so is aging associated with decreased testosterone production in men. In this chapter, Pike and Rosario review novel and compelling data indicating testosterone regulation of β-amyloid production in the brain, as well as significant associations between low testosterone levels and risk for Alzheimer's-related dementia in men. Based on these data and on the various mechanisms by which testosterone can exert neuroprotective effects in brain, the authors conclude that low testosterone is a likely risk factor for Alzheimer's-related dementia in men. Their analysis points out the need for research focusing on the development of brain-selective androgen receptor modulators (SARMs) for use in the prevention of Alzheimer's disease (AD) in men.