In 1999, at the direction of Congress, the National Institute on Aging (NIA), in conjunction with the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Mental Health (NIMH), and the National Institute of Nursing Research (NINR) embarked on the Alzheimer's Disease (AD) Prevention Initiative. An important part of the AD Prevention Initiative is to quicken the pace for translating basic science findings into clinical trials to evaluate treatment and prevention strategies. This Program Announcement (PA) focuses on AD drug discovery while a companion PA is targeted to AD pilot clinical trials.