Vasanthy Narayanaswami, Ph.D.
Children’s Hospital Oakland Research Institute
Oakland, California

2003 T. L. L. Temple Foundation Discovery Award

Scientists have discovered several genes that cause rare, inherited forms of early-onset Alzheimer’s disease, but only one gene has been found to contribute to an increased risk of the more common, late-onset form of the disease. The late-onset risk gene, APOE, comes in several forms, one of which somewhat increases the risk that a person will develop Alzheimer’s. Apolipoprotein E, the protein produced by the APOE gene, plays a critical role in the regulation of fat and cholesterol, which have recently been linked with the prime suspect in Alzheimer’s, the protein fragment beta-amyloid.

Vasanthy Narayanaswami, PhD, and colleagues will investigate the relationship between apoliprotein E, beta-amyloid, and cholesterol. Under laboratory conditions, the researchers will use advanced chemistry to manipulate and observe interactions among the three molecules. They hope to discover whether APOE-e4, the gene associated with increased Alzheimer risk, produces a form of apolipoprotein E that interacts in distinct ways with beta-amyloid and cholesterol. They also hope to learn whether these interactions help explain why beta-amyloid tends to aggregate by stages into toxic “fibrils” and, ultimately, the large deposits called plaques found among brain cells in Alzheimer’s disease.