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2005 Grant - Raber

Neurogenesis and Cognition in Irradiated APOE Mice

Jacob Raber, Ph.D.
Oregon Health & Science University
Portland, Oregon

2005 Investigator-Initiated Research Grant

Radiation exposure to the brain during medical treatment may have adverse effects, including cognitive impairment. Studies with mice have shown that radiation overexposure results in cell injury or loss in a region of the brain important for learning and memory.

Jacob Raber, Ph.D., and associates are investigating (1) whether a genetic risk factor associated with Alzheimer's disease is also associated with injury due to radiation exposure or (2) whether radiation exposure in genetically at-risk people results in earlier onset or more rapid progression of Alzheimer's.

The APOE gene is found most commonly in three forms: APOE-e2, APOE-e3 and APOE-e4. APOE-e4 is associated with an increased risk of developing Alzheimer's disease. In preliminary studies with mice that are genetically altered to carry some form of human APOE, Dr. Raber's group has observed cellular dysfunctions resulting from radiation exposure and evidence that type of APOE is associated with the degree of injury.

In the current study with mice, the investigators will examine how APOE type is related to (1) the extent of cell loss, (2) the degree of neuronal recovery or repair, (3) changes in memory and learning skills, (4) the degree of certain types of cell damage and (5) the ability of an antioxidant to alleviate radiation-induced injury. The findings may clarify risks associated with radiation treatment in humans and strategies for preventing or treating radiation injury.