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2010 Grants - Murphy
Leptin Resistance and Alzheimer's Disease
Michael Paul Murphy, Ph.D.
University of Kentucky Research Foundation
2010 Investigator-Initiated Research Grant
The risk of Alzheimer's disease is linked to obesity and type 2 diabetes, although the mechanisms explaining this link are not understood. One possible mechanism involves the hormone leptin. Leptin is released by fat cells in the body and acts on the brain to regulate hunger. Leptin has also been shown to reduce the production of beta-amyloid, a protein fragment at the focus of research into the causes of Alzheimer's disease.
Michael Paul Murphy, Ph.D., and colleagues are studying a possible link between an increased risk of Alzheimer's disease and the presence of obesity or type 2 diabetes. This link arises from the fact that persons with obesity or type 2 diabetes also have high levels of beta-amyloid, despite having high levels of leptin. Dr. Murphy and colleagues are examining the idea that this occurs because these individuals have become resistant to leptin—that is, the leptin receptors in their brain no longer respond to the presence of leptin. To examine this possible link, the researchers will create a strain of mice that have genetic characteristics of obesity-related diabetes, leptin resistance and Alzheimer-like pathology. Experiments conducted on these mice will allow the researchers to determine if leptin resistance is the molecular mechanism that links obesity and type 2 diabetes to an increased risk of Alzheimer pathology. These studies will advance our understanding of how diabetes and obesity increase an individual's risk of Alzheimer's disease.