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2016 Grants - Shih
Long-term In Vivo Imaging of the Pericyte Response to Amyloid Beta
Andy Shih, Ph.D.
Medical University of South Carolina
Charleston, South Carolina
2016 New Investigator Research Grant
How does beta-amyloid affect the function of blood vessels in the brain?
Pericytes are cells that form the outer layer of small blood vessels throughout the body. They can contract and expand to control blood flow, and are also involved in many other aspects of blood vessel function. In the brain, they are an essential component of the blood-brain barrier, a specialized structure which controls what types of molecules are allowed to enter the brain.
There is evidence that alterations in the function of the blood-brain barrier and changes in the brain’s blood flow are important factors in the development of Alzheimer’s disease. Scientists believe dysfunction of pericytes may contribute to the disease process. Unfortunately, scientists have not yet had methods for studying pericytes in the living brain, making it challenging to understand the role they may play in Alzheimer’s disease.
Andy Shih, Ph.D., and colleagues have developed genetically-engineered mice in which the pericytes can be identified with a fluorescently tagged protein. Using a specialized microscopy technique called “two-photon” imaging, the researchers can visualize changes in the structure and location of perictyes in the brains of the living animals, allowing real-time changes to be observed.
Dr. Shih and colleagues will use this technique to visualize how pericytes in the brain respond to beta-amyloid. Beta-amyloid is a protein fragment known to be toxic to nerve cells and strongly implicated in Alzheimer’s disease. The researchers plan to study how beta-amyloid affects the ability of pericytes to control blood flow in the brain, as well as its ability to alter the blood-brain barrier.
Dr. Shih’s research will explore links between some of the fundamental mechanisms thought to be involved in Alzheimer’s disease and vascular changes in the brain. The work may reveal the role of pericytes in the disease process, as well as possible ways to preserve pericyte function. A better understanding of the changes in pericyte function could inform the development of new treatments for Alzheimer’s disease.