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2011 Grants - Pimplikar
Inflammation and Microglial Activation in AICD Transgenic Mice
Sanjay W. Pimplikar, Ph.D.
2011 Multi-Centered Project Grant-Component Project
Note: This is one part of a multi-part description. For an introduction to some of the concepts mentioned here, please read the document Lamb and Colleagues Overview.
Much research into the causes of Alzheimer's disease has focused on the role of beta-amyloid, a protein fragment that accumulates outside of nerve cells to form amyloid plaques, one of the hallmarks of Alzheimer's pathology. Beta-amyloid is created when a larger protein, amyloid precursor protein (APP), is cut into pieces. When this happens, another fragment of APP is left inside the nerve cell. This fragment is known as the APP intracellular domain (AICD).
Sanjay W. Pimplikar and colleagues have been studying the role of AICD in mice that have been genetically altered to have higher amounts of this protein fragment, without having high levels of beta-amyloid. They have found that such mice exhibit many features of Alzheimer's disease, including inflammation in the brain and memory impairment.
Dr. Pimplikar and colleagues have proposed a series of studies to examine how AICD causes inflammation in the brain. They will use genetic engineering techniques to create strains of mice in which signaling molecules that activate either microglia or monocytes (see Overview) are turned off. Using such mice, the researchers will determine which aspects of brain inflammation are caused by microglia and which aspects are caused by monocytes. These studies will help to define the mechanisms of inflammation in Alzheimer's disease, and they may provide insights into ways to prevent inflammation that contributes to neurodegeneration.