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2006 Grant - Wyrwicz
Effect of ApoE Isoform on Hippocampal Microstructure and Function
Alice M. Wyrwicz, Ph.D.
Evanston Northwestern Healthcare Research Institute
2006 Investigator-Initiated Research Grant
Sporadic, or noninherited Alzheimer's disease, is by far the most common form of this deadly disorder. Though the exact cause of sporadic Alzheimer's is still unclear, there are certain risk factors that have been linked to the disease. One of the most powerful is a cholesterol-binding protein called apolipoprotein E, which comes in three common forms, abbreviated ApoE2, ApoE3 and ApoE4. Though scientists are still debating why, people with the ApoE4 form are at increased risk for getting Alzheimer's disease. ApoE4 has also been associated with impairments in learning and memory-cognitive skills that characteristically deteriorate as Alzheimer pathology progresses.
Alice Wyrwicz, Ph.D., and colleagues plan to generate a new animal model that can be used to explore the links between ApoE, cognition and Alzheimer's disease. The investigators will systematically replace the mouse ApoE gene with one of the human forms. They will then compare how each human ApoE affects learning, memory and the structure of the hippocampus, a part of the brain that is intimately associated with learning and memory, and one of the first regions to be damaged in Alzheimer's.
The researchers will test learning and memory in the mice using specifically designed mazes. They will examine their brains for changes to the hippo-campus using a relatively new and sophisticated form of magnetic resonance imaging called diffusion tensor imaging. This research may not only help uncover the role of ApoE in Alzheimer's, but it may lead to an earlier test for the disease. Currently, doctors rely primarily on cognitive tests for diagnosis, which means that damage to the brain is already well under way by the time Alzheimer's disease is confirmed. But diffusion tensor imaging may have the potential to detect subtle changes in brain tissue before there is any loss in cognitive abilities.