The vast majority of people who develop Alzheimer’s disease (AD) are age 65 or older. The aging of the baby boom generation will significantly increase the number of people in the world with AD, which has been described as an advancing “silver tsunami.” However, AD is not a normal part of aging, and older age alone is not sufficient to cause this disease. Aging is, however, the major risk factor, and we believe that understanding how the brain ages will allow us to devise ways to better protect it against AD. We propose that certain brain cells are especially vulnerable to aging, and this makes them more likely to go awry in older age, leading to the cascade of events that results in AD. The aging process is poorly understood, and its impact very often is not taken into account in molecular and cellular studies of AD, making the effect of therapeutics administered to the elderly unpredictable. We propose to use novel, sophisticated, state-of-the-art methods to identify what changes occur in individual brain cells, which will lead us to understand how aging predisposes the brain to develop AD, and how to better protect it.