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2007 Grant - Pautler
Neuroimaging Assessment of the Role of GM2 in Alzheimer's Disease
Robia G. Pautler, Ph.D.
Baylor College of Medicine
2007 New Investigator Research Grant
GM2 is a large and complex biological molecule composed of sugar and lipid components. It is normally produced and metabolized in the body, but some individuals have genetic disorders that interfere with the metabolism of GM2. Such disorders cause GM2 to accumulate in nerve cells, leading to cell death. There is also some evidence that GM2 may play a role in Alzheimer's disease. For example, GM2 binds to beta-amyloid, a protein fragment that accumulates in the brains of people with Alzheimer's.
Another pathologic feature of Alzheimer's disease is the disruption of nutrient transport in nerve cells. There is also some evidence, from studies of nerve cells growing in culture, that GM2 may disrupt such nutrient transport. The effects of GM2, however, are poorly understood and have not been studied in much detail.
Robia Pautler, Ph.D., and colleagues plan to study the effects of GM2 in the brain and how they might be related to Alzheimer pathology. They will use magnetic resonance imaging (MRI) to study the accumulation of GM2 in the brain and assess how such accumulation affects nutrient transport in nerve cells. They will also study whether GM2 promotes the accumulation of beta-amyloid in the brain. For these studies, they will use mice that have been genetically altered to express many of the pathologic features of Alzheimer's disease. These studies may help to clarify the fundamental pathologic mechanisms of Alzheimer's disease and may lead to the development of new treatment strategies.