New Research Project to Examine the Role of Microglia in Alzheimer’s Disease Using Cellular Reprogramming

The John Douglas French Alzheimer's Foundation has funded an important new research project under the direction of Justin Ichida, PhD, of the University of Southern California, Department of Stem Cell Biology and Regenerative Medicine. 

The research project—Examining the Role of Microglia in Alzheimer’s Disease Using Cellular Reprogrammingapplies new techniques to enable researchers to gain a better understanding of how genetic differences affect the functioning of Microglia, and the risk for Alzheimer’s disease.

Microglia are a type of immune cell that make up about 15% of the cells in the brain. Microglia scavenge throughout the central nervous system removing infectious agents, damaged neurons, and plaques. Interestingly, recent studies suggest that genetic differences that increase the risk of developing Alzheimer’s disease (AD) may do so by altering microglial function rather than nerve cell function. This is because many of the genes or gene control regions that have been recently linked to AD are predicted to predominantly affect microglia. 

However, studying how AD-associated genetic changes affect human microglial function has been challenging because obtaining microglia from biopsies is difficult. To address this problem, Dr. Ichida and his team have developed a method called “cellular reprogramming” that enables the generation of human microglia from biopsied skin or blood cells. This approach has been used to produce functional nerve cells and other cell types from patients, but not microglia. Dr. Ichida’s team will couple this procedure with a technique called CRISPR that allows the introduction of genetic changes that increase AD risk into microglia in a petri dish. 

The research project will test the hypothesis that genetic differences that increase AD risk do so in part by altering microglial function. They will do this by examining microglial function in the presence or absence of two different genetic changes that are strongly associated with AD. The impact of this study will be to 1) determine if AD-associated genetic changes cause disease-relevant alterations in human microglial function and 2) establish this approach as a powerful platform for studying the role of microglia in AD.