2004 Investigator-Initiated Research Grant

A tiny protein fragment called beta-amyloid is a key suspect in Alzheimer’s disease processes that damage cell-to-cell communication and destroy cells in the brain. One therapeutic strategy is to create a “vaccine” based on a modified version of beta-amyloid that trains the immune system to recognize and attack the protein fragment. Early-stage human trials of such a vaccine were stopped when some participants developed severe inflammation in the brain, but follow-up of participants continues to provide valuable information about the vaccine’s long-term effects.

The adverse side effects in these trials may have been the result of immune-system T cells that react specifically to beta-amyloid. Alon Monsonego, Ph.D., and colleagues are studying these beta-amyloid–reactive T cells, not only for their potential role in treatments but also for their “normal” role in aging and Alzheimer’s disease. This research team has observed T cell reaction to beta-amyloid in both older healthy adults and people with Alzheimer’s, while there is little evidence of such reaction in middle-aged adults.

In this study, the investigators will examine this issue in genetically altered mice that develop an Alzheimer-like disorder. These mice have an age-associated T cell reaction to beta-amyloid but do not develop immune-system antibodies to the protein fragment. This model should enable the researchers to exam the role of T cells in a more controlled environment.

The researchers will characterize T cell reaction to beta-amyloid in the mouse model and determine whether it is beneficial or only contributes to disease processes. This work may lay the foundation for examining factors that influence T cell reactivity in normal aging, Alzheimer’s disease, and Alzheimer vaccine treatments.