2004 Investigator-Initiated Research Grant

Increasing age is the greatest known risk factor for developing Alzheimer’s disease. Therefore, normal changes in the body associated with aging are of particular interest because they may explain why a vulnerability to Alzheimer pathology is linked to aging.

Christian J. Pike, Ph.D., and colleagues are investigating how normal age-related depletion of androgens, a class of hormones that includes testosterone and other male sex hormones, may make brain cells more vulnerable to damage. In previous studies, they have examined two possible functions of androgens in the brain: (1) protecting and helping maintain the health of nerve cells and (2) helping regulate the production of beta-amyloid, a tiny protein fragment that is a key suspect in Alzheimer’s disease.

In this study, the investigators will examine autopsied human brain tissues to determine if age-related depletion of androgens is associated with increased levels of beta-amyloid. They will also assess this possible association in aging male mice that develop amyloid deposits.

They researchers will study the interaction of aging, androgen loss, and nerve cell vulnerability in mice, as well as the ability of androgen replacement therapy to restore protective functions. Using mice that develop an Alzheimer-like disorder, they will assess how the manipulation of androgen levels affects disease progression.

The outcome of this work may help clarify how aging is related to the risk of Alzheimer’s disease and suggest new therapeutic strategies to protect cells from disease-related damage.