Jean-Charles Lambert, Ph.D.
Institute Pasteur de Lille
Lille, France

2006 Investigator-Initiated Research Grant

The molecular mechanisms of Alzheimer's disease are not well understood. One variant gene form is known to increase a person's risk for late-onset Alzheimer's disease. Researchers believe that other genes may contribute to a person's susceptibility or account for other forms of the disease.

Jean-Charles Lambert, Ph.D., and colleagues have performed a series of screening studies with the goal of identifying additional genes that might be associated with an increase in the risk of Alzheimer's disease. With these studies, the researchers identified an unexpected gene that appears to be associated with Alzheimer's. This gene, which codes for the protein ornithine transcarbamylase (OTC), was expressed in the brain of 12 individuals with the disease but in no patients without the disease.

The OTC protein is an enzyme that is a part of a biochemical cycle involved in detoxification of waste products. That cycle is known as the urea cycle. This cycle is not usually active in the brain, so it was unexpected that the OTC gene would be expressed in the brain of a person with Alzheimer's disease.

The researchers will continue their study of the OTC gene in Alzheimer's disease to confirm their original findings. They will also extend their studies to look for other enzymes that are part of the urea cycle to determine if those other genes are also expressed in the brains of people with Alzheimer's disease. These studies may help to identify new genes associated with an increase in the risk of Alzheimer's.