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How do the brain’s support cells contribute to risk for Alzheimer’s?
Aiqun Li, Ph.D.
Icahn School of Medicine at Mount Sinai
New York, NY - United States
Background
The immune system is complex and works to maintain our health. Microglia are the primary immune cells in the brain, and work to maintain healthy nerve cells by removing unwanted molecules in the brain, along with other functions. Problems within the immune system, including increased activity of microglia, can lead to brain inflammation, which is common in individuals with Alzheimer’s.
Another factor that can contribute to Alzheimer’s is an individual's genes (coded for in their DNA). Current research focuses on how genes interact with other factors, like the immune system, to increase or decrease one's risk of Alzheimer’s. Many of the genes identified related to risk have been linked to the microglia. Understanding how the microglia and risk genes interact will help increase the understanding of the unique role they play in Alzheimer’s.
Research Plan
Dr. Li and colleagues will use a specialized type of stem cell collected from adult human tissue called hiPSCs (human induced Pluripotent Stem Cells). These hiPSCs are from adult cells that can be reprogrammed into any type of cell in the human body including microglia. Using microglia generated from these cells, the research team will study the role specific risk genes previously identified may play in microglia’s activity. By turning genes “on” and “off” through a gene editing technique called CRISPR (which allows the researcher to manipulate the gene for increased or decreased activity), they research team will look at microglia’s ability to remove unwanted proteins from the brain through a process called phagocytosis, which is the engulfing of foreign material by the microglia. They will also track how the rest of the microglia responds to certain genes being turned on or off.
Impact
This research will help provide information on the role microglia may play in Alzheimer’s, and improve our understanding of how this biology intersects with identified genes that increase/ decrease risk. A greater understanding of the microglia may open the door for novel therapies to be explored.
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