2004 New Investigator Research Grant

Beta-amyloid is a protein fragment that may be a key factor in damaging cell-to-cell communication and causing the loss of brain cells in Alzheimer’s disease. The presence of beta-amyloid results in the activation of microglia, specialized immune-system cells in the brain.

Microglia may be beneficial by “devouring” beta-amyloid and releasing proteins that protect cells and promote cell growth. However, microglia may also contribute to disease processes by enlisting immune-system cells that lead to long-term inflammation. Timothy J. Seabrook, B.M.L.Sc., Ph.D., and colleagues have hypothesized that the beneficial effects of microglia occur early in the course of Alzheimer’s disease, and that the harmful effects happen later.

The investigators will test this hypothesis in mice that are genetically altered to carry human Alzheimer-related genes and that begin developing amyloid deposits at about five months (adulthood). They will assess amyloid levels and evidence of inflammation in mice these, then begin a three-month regimen of a microglia-suppressing compound at either four or 12 months of age.

In a related experiment, the researchers will study a combination therapy of the microglia-suppressing compound and an Alzheimer “vaccine” that clears beta-amyloid from the brain but also results in inflammation. Some mice will receive the vaccination only and some the combination therapy.

The outcome of this research may clarify the complex role of microglia in Alzheimer’s, demonstrate the potential therapeutic benefit of regulating microglia at certain times in the disease process, and establish a foundation for testing combination anti-amyloid treatments.