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2007 Grant - Smith
Aging-Accelerated Mice to Study Mild Cognitive Impairment/Early Alzheimer's Disease Event Chronology and Therapy
Gemma Casadesus Smith, Ph.D.
Case Western Reserve University
2007 New Investigator Research Grant
Alzheimer's disease is a progressive brain disorder that involves changes to the structure of nerve cells over time. However, scientists do not yet know the exact chronology of these changes. To better understand the biological mechanisms underlying Alzheimer progression, scientists have used mice genetically altered to develop Alzheimer-like pathology and symptoms. One such mouse model has been engineered to age prematurely.
For their proposed grant, Gemma Casadesus Smith, Ph.D., and colleagues will use prematurely aging mice to study three early degenerative "events" in Alzheimer's disease. One of these events is the production of abnormally structured tau protein. Abnormal tau tends to accumulate into harmful tangles that are a hallmark of Alzheimer's. The second event is the development of oxidative stress, or damage to cell structures by toxic oxygen molecules called free radicals. The third event involves the stimulation of nerve cells to enter the cell division cycle. Nerve cells usually die when they are induced to divide. Dr. Smith's team will first determine the exact chronological appearance of these events in the mice. The researchers will then administer drug therapies to some of their animals to test whether the therapies (1) alter any of the three Alzheimer pathological features or (2) improve the rodents' cognitive abilities.
Results of this study should help clarify how Alzheimer's disease progresses in its early stages and how individual features of the disease contribute to that progression. Ultimately, the study could lead to new therapies for preventing and treating Alzheimer's.