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2022 Alzheimer's Association Research Grant (AARG)

Role of MAIT cells and MR1 in AD Development

How can an immune system cell in the brain promote Alzheimer’s disease brain changes?

Randy Brutkiewicz, Ph.D.
Indiana University
Bloomington, IN - United States


Recent studies have shown that Alzheimer’s may be linked to changes in the innate immune system, the part of the immune system that responds in a general way to foreign substances. Damage to this system may, for example, hinder the brain’s ability to clear harmful beta-amyloid, a protein fragment that accumulates into plaques, a hallmark of Alzheimer’s.

One important cell type in the innate immune system is called the mucosal associated invariant T (MAIT) cell. MAIT cells help protect the body from harmful bacteria and other microbes. MAIT cells are turned “on” in part, by a protein called the major histocompatibility complex class 1-related gene protein (MR1). Recent studies have found that MAIT cell and MR1 protein activity may become abnormal during Alzheimer’s and related dementias.

In initial research, Dr. Randy R. Brutkiewicz and colleagues found that MR1 is turned on in the brains of genetically engineered Alzheimer’s-like mice, as well as in brain tissue from individuals who had Alzheimer’s. However, the exact role that MR1 protein and MAIT cells play in Alzheimer’s is unknown.

Research Plan

To better understand this role, Dr. Brutkiewicz and team will conduct a larger study of MAIT and MR1 in Alzheimer’s. First, they will examine Alzheimer’s-like mice engineered to lack MR1 protein and MAIT cells. Using brain scan techniques, they will determine how the removal of MR1 and MAIT cells may impact certain disease-related changes, such as brain cell loss. Then, using another brain scan technique, the researchers will determine if the number of MAIT cells with MR1 is higher in brain tissue from individuals who had Alzheimer’s than individuals who did not. They will also assess how MAIT cells interact with other cells involved in the immune system, and how increased MR1 activity may relate to beta-amyloid plaques. 


Results from this project could refine our understanding of how immune system dysfunction and dementia are linked. They could also lead to novel disease therapies.

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