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2014 Grants - Blurton-Jones
Examining the Role of TREM2 in Alzheimer’s Pathogenesis With iPSC-Derived Microglia
Mathew Mark Blurton-Jones, Ph.D.
University of California, Irvine
2014 Investigator-Initiated Research Grant: Biological Underpinnings of Genetic Risk Factors in Alzheimer’s
Microglia are an important type of immune cell in the brain and are thought to be involved in brain inflammation that is a common feature of Alzheimer’s disease. TREM2 (triggering receptor expressed on myeloid cells 2) is a protein found on the outside surface of microglia and other immune cells that is involved in regulating inflammatory pathways. Recent studies have found that certain variations in the gene for TREM2 are a strong risk factor for developing Alzheimer’s disease. However, the function of TREM2 and its possible role in Alzheimer’s disease are poorly understood.
Beta-amyloid is a protein fragment strongly implicated in Alzheimer’s disease, and healthy microglia are important for removing it from the brain. To help understand how alterations in TREM2 might impact the function of microglia in Alzheimer’s disease, scientists can use special cells that can be converted into many other types of cells, such as microglia, a characteristic described as “pluripotent.” One type of these cells, known as induced pluripotent stem cells (iPSCs) can be obtained directly from adult skin cells.
Mathew Mark Blurton-Jones, Ph.D., and colleagues have proposed to use iPSCs to study the role of TREM2 in the development of Alzheimer’s disease. Using iPSCs, the researchers will use molecular techniques to alter the TREM2 gene. The iPSC cells with altered TREM2 genes will be converted into microglia and their function studied in mice engineered to develop an Alzheimer’s-like condition. Dr. Blurton-Jones and colleagues will study how these microglia function in the brain, including how they remove beta-amyloid from the brain. These studies will provide important clues about the function of TREM2 and why mutations of the TREM2 gene are a strong risk factor for Alzheimer’s disease, possibly paving the way for new approaches for slowing or halting disease progression.