# Regulatory T Cells in Alzheimer's Disease

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2022 · $364,654

## Abstract

PROJECT SUMMARY
Recent studies have demonstrated that the adaptive immune response plays an important role in the process
of Alzheimer’s disease (AD) progression by promoting a pro-inflammatory state in the brain. This inflammatory
process involves both T cell and microglial cell activation. Such inflammatory processes are typically
suppressed by a subset of T cells called regulatory T cells (Tregs). Tregs have been found to accumulate in
the brains of patients with Alzheimer’s disease or in the brains of mice engineered to develop. Previous studies
have demonstrated that systemic depletion of Tregs exacerbates AD pathology, while an increase in Tregs
attenuates AD pathology in transgenic mouse models of AD. However, a major caveat associated with the
systemic Treg depletion studies is that they deplete Tregs everywhere and induce body-wide inflammation.
This makes it difficult to assess whether worse outcomes observed in AD upon Treg depletion are specific to
an effect of Tregs in the brain or simply due to massive systemic inflammation. In addition, the types of Tregs
that accumulate during AD progression, and their functional role in disease progression, are also unknown.
Thus, major gaps in our knowledge are (i) what types of Tregs are found in the brain during steady-
state and in Alzheimer’s disease and, (ii) what role distinct subsets of Tregs play in ameliorating AD.
As part of the parent grant, we have demonstrated that Tregs in tissues can be quite diverse and that distinct
Treg subsets occupy inflamed tissues with different kinetics. Most notably, we identified a novel population of
Tregs, called ISG-Tregs, that accumulate in tissues with IFN-driven inflammation. Previous studies of AD
demonstrate that type I IFN is a characteristic of AD, that it exacerbates neurological damage in AD models,
and plays an important role in initiating neuroinflammation and promoting AD progression. Thus, ISG-Tregs
may play a critical role in AD progression. The goal of this research supplement is to identify the distinct
subsets of Tregs present in the brain during AD progression, identify where those Treg subsets are
located within the brain during AD progression, and establish murine models that will allow us to
directly test the function of Tregs and Treg subsets in AD. We will use scRNA-Seq and spatial
proteomic/transcriptomic approaches to characterize Tregs during AD progression. Using a novel Treg
reporter/delete mouse strain that we developed we will also develop new mouse models that will allow us to
study the function of brain Tregs, or select brain Treg subsets, on AD progression. These studies will allow us
to characterize the types of Tregs present in Alzheimer’s disease, establish their localization in the brain during
disease progression, and develop models that will allow us to establish their functional role in ameliorating or
exacerbating Alzheimer’s disease in the future. Such information will prove critical for better implementation ...

## Key facts

- **NIH application ID:** 10498857
- **Project number:** 3R01AI124512-07S1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Michael Archibald Farrar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $364,654
- **Award type:** 3
- **Project period:** 2016-03-15 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10498857

## Citation

> US National Institutes of Health, RePORTER application 10498857, Regulatory T Cells in Alzheimer's Disease (3R01AI124512-07S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10498857. Licensed CC0.

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