How do different forms of the APOE gene affect cells in the brain, in Alzheimer’s?
Duke University Medical Center
Durham, NC - United States
Apolipoprotein E (APOE) is a gene that can produce several different types of the ApoE protein. One form of the APOE gene known as APOEe4 is a known risk factor for Alzheimer’s, whereas another form, APOEe2, is thought to provide reduced risk for Alzheimer’s. The underlying mechanisms by which different versions of the APOE gene affect Alzheimer’s risk are as yet unknown. There are indications that APOE may change the way other genes are turned on and off as individuals age.
Dr. Lidia Tagliafierro believes that the contribution of cross talk between different cell types may represent a key factor in the onset and progression of Alzheimer’s. To address this question, Dr. Tagliafierro proposes to use adult human induced pluripotent stem cells (hiPSC) - that are special cells grown on laboratory dishes programmed to develop into any type of cell - to determine the role of APOE gene variations in nerve cells and immune cells called microglia.
Dr. Tagliafierro will produce genetically engineered stem cells from adults, each containing one variation of the APOE gene (APOEe2, APOEe3, or APOEe4). These cells will then be programmed to develop into either nerve cells or microglial cells that contain a version of the APOE gene.
To reproduce what occurs in the aging brain, the researchers will allow these nerve cells and microglial cells to grow together over time in laboratory dishes, using different combinations of both cells containing the gene variations. For each nerve cell/microglial cell combination, Dr. Tagliafierro will determine which genes are turned on and off, and whether there are any changes in how the cells communicate with each other and how they function.
These studies will provide new information regarding how APOE variations affect nerve cells and microglial cells in the brain, and how the effect of APOE changes with age. These studies may also identify new opportunities for developing therapies that will slow the onset and progression of Alzheimer’s.
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