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2017 Grants - Chow
Targeting Brain Insulin Resistance-mediated Neuronal Dysfunction in AD
Hei-Man Chow, Ph.D.
The Hong Kong University of Science and Technology
Kowloon, Hong Kong
2017 Alzheimer's Association Research Fellowship (AARF)
How are high levels of insulin in the brain related to the development of Alzheimer's disease?
The molecule insulin is produced by the body after a meal to help move nutrients (glucose) from the blood stream into the body's tissues and cells where it can be used for energy. When the body's cells are unable to recognize insulin—a condition called insulin resistance—and glucose remains in the blood stream, the body attempts to produce more insulin to compensate. As a result, individuals with insulin resistance develop high levels of glucose and insulin in the blood. These individuals are also twice as likely to develop Alzheimer's disease, but the connection between insulin resistance and Alzheimer's disease is not known.
Hei-Man Chow, Ph.D., and colleagues propose to determine the effect of high insulin levels on nerve cells in the brain. They observed that mice with high levels of insulin in the blood also have high levels of insulin in the brain, and that nerve cells in the brain develop insulin resistance. They also found that nerve cells in a laboratory dish that are treated with high levels of insulin for long periods of time stop growing and have high levels of the protein fragment beta-amyloid, a characteristic of Alzheimer's disease.
Dr. Chow and colleagues propose to identify the molecules within the nerve cells of the brain that are affected by insulin resistance and how these changes interfere with nerve cell growth and function. They will also test whether a drug known to improve insulin resistance, Liraglutide, can improve nerve cell growth and function. Finally, they will treat mice that are genetically engineered to develop an Alzheimer's disease-like condition with Liraglutide, and measure the effect on memory and learning, insulin resistance, and growth and function of nerve cells in the brain.
This study may help reveal the connection between insulin resistance in the nerve cells of the brain with the development of Alzheimer's disease. It may also reveal insights into whether treatment of insulin resistance with Liraglutide can prevent the detrimental effects of high insulin levels on the nerve cells in the brain and improve memory and learning.