# Analysis of the MR1/MAIT cell axis in a murine model of Alzheimers disease

> **NIH NIH R21** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $435,875

## Abstract

Alzheimer’s disease (AD) is a rapidly-growing and serious worldwide malady, which is currently the most
common cause of dementia in patients of advanced age. Patients develop brain pathology mediated by the
amyloid β (Aβ) protein, the function of which has recently been reported to include a type of host defense against
microbial invaders of the brain, as part of the innate immune response. One component of the innate immune
response that is important against microbial infections is the MR1/MAIT cell axis. MR1 is a major
histocompatibility complex class I-like molecule that presents microbial vitamin B-derived metabolites to an
invariant T cell subpopulation called, “mucosal-associated invariant T (MAIT) cells”. We have found that MR1
gene expression is upregulated in the temporal cortex of both AD patients and 8-month old 5XFAD (AD model)
mice. Moreover, MAIT cells can be found in the brains of normal, wildtype mice. The MR1 protein is expressed
on the surface of astrocytes and microglia isolated from the brain, and each cell type is capable of presenting
microbial antigens that activate MAIT cells in an MR1-dependent manner. Considering the variety of studies
that have reported defects in the blood-brain barrier in the elderly, AD patients and AD mouse models, along
with the presence of infectious agents in the AD brain and putative anti-microbial role for Aβ, we are focused on
understanding the role of the MR1/MAIT cell axis in AD pathology development. For this, we will use the 5XFAD
AD mouse model system. Our hypothesis is that the MR1/MAIT cell axis contributes to AD pathology. As a
result, we predict that in an MR1-deficient environment (i.e., MR1 knockout 5XFAD mice), there will be an
attenuation of AD symptoms. To address this hypothesis, we have proposed the following two Specific Aims:
1. Determine the functional capacity of brain cells from 5XFAD mice to stimulate MAIT cells in an MR1-restricted
manner; 2. Define AD development in MR1-deficient 5XFAD mice. These studies will allow us to determine the
contribution of the MR1/MAIT cell axis in AD development, using this mouse model. We then will use what we
learn here as a springboard to the development of more in-depth mechanistic studies, focused on role of this
innate immune axis in AD.

## Key facts

- **NIH application ID:** 10152141
- **Project number:** 1R21AG071269-01
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Randy R Brutkiewicz
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $435,875
- **Award type:** 1
- **Project period:** 2020-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10152141

## Citation

> US National Institutes of Health, RePORTER application 10152141, Analysis of the MR1/MAIT cell axis in a murine model of Alzheimers disease (1R21AG071269-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10152141. Licensed CC0.

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