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2008 Grant - Lesort
Pathological Interactions in Diabetes and Alzheimer's Disease
Mathieu Lesort, Ph.D.
The University of Alabama at Birmingham
2008 Investigator-Initiated Research Grant
Recent studies have found close relationships between Alzheimer's disease and diabetes. Diabetes occurs when the hormone insulin becomes unable to perform one of its most important functions—regulating the body's use of glucose (sugar). This condition, also called insulin resistance, can lead to impaired brain function. In fact, studies suggest that diabetics have almost twice as great a risk of acquiring Alzheimer's as do non-diabetics. Yet the exact links between insulin resistance and brain disorders have not been fully identified.
Mathieu Lesort, Ph.D., and colleagues have been studying the role of tau protein in both Alzheimer's and diabetes. Tau is a naturally occurring substance that helps maintain the structural framework and transport system within brain cells. This protein is normally modified by the attachment of phosphate molecules, a process called phosphorylation. However, tau becomes excessively phosphorylated in Alzheimer's disease, and it accumulates into tangles that prevent the protein from carrying out its normal functions. In preliminary research, Dr. Lesort's team has found that tau also becomes excessively phosphorylated in mice engineered to develop diabetes. The team hypothesizes that excessive tau phosphorylation in diabetic brains predisposes these brains to acquiring Alzheimer's.
Dr. Lesort and colleagues plan to test their hypothesis using mice genetically altered to produce Alzheimer-like symptoms. They will induce diabetic pathologies in these mice, including excessively phosphorylated tau, and analyze whether such pathologies affect Alzheimer development.
Results of Dr. Lesort's study could shed new light on the biological mechanisms underlying both Alzheimer's and diabetes.