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2011 Grants - Lamb
The Role of Mononuclear Phagocytes in Tauopathies
Bruce T. Lamb, 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.
Tau is a protein that helps maintain the structure of nerve cells and transport nutrients within cells. In several neurodegenerative conditions, including Alzheimer's disease, tau becomes modified by the addition of excessive chemical phosphate groups (phosphorylation). When modified in that way, tau proteins form abnormal structures known as neurofibrillary tangles, which are one of the hallmarks of Alzheimer's pathology. Abnormal modifications of tau that are associated with disease are collectively known as tauopathies.
Bruce T. Lamb and colleagues have been studying the role of mononuclear phagocytes (MNPs; see Overview) in the development of tauopathies. They have proposed to study how two types of MNPs, microglia and monocytes, contribute to this process. Using mice that have been genetically altered to exhibit excessive phosphorylation of tau, the researchers will examine the localization and activity of microglia and monocytes. These studies rely on the use of a special tag that is expressed in the cells allowing them to be visualized under a microscope with special fluorescent lighting. Dr. Lamb and colleagues will study when activated monocytes and microglia appear and how they are localized in the brain of mice during the development of tauopathy.
Dr. Lamb's team will also study the role of a specific receptor on the surface of monocytes. This receptor, known as CCR2, responds to hormone-like substances and directs monocytes to enter the brain, where they may contribute to inflammation and tauopathy. The researchers will use genetic techniques to remove CCR2 and then study whether tauopathy is diminished. These studies will provide new insights into the role of MNPs in the development of tauopathy, including neurofibrillary tangles found in Alzheimer's disease.