# The Role of Regulatory T Cells in Alzheimer's Disease

> **NIH NIH F30** · UNIVERSITY OF MINNESOTA · 2024 · $53,974

## Abstract

PROJECT SUMMARY
Alzheimer’s disease (AD) is the most common type of dementia, afflicting approximately 5.7 million people, or
60–80% of cases of dementia in the United States, and is predicted to triple to 16 million by the year 2050.
Diagnosis is made after the age of 65 in 90-95% of patients, with the remaining 5-10% considered early-onset.
Symptoms usually begin with difficulty learning new facts or recalling recent memories. In the middle stage of
AD progression, language becomes more difficult, memory continues to deteriorate with long-term memory
now also being affected, patients may not recognize close relatives, and will need assistance with most
activities of daily living. During the late stage of AD, language is eventually lost, muscle atrophies to the degree
that patients cannot get out of bed or feed themselves, and pneumonia or infection of pressure ulcers usually
leads to death. Thus, AD is clearly a significant health problem. The biochemical basis for AD pathophysiology
is thought to be the aggregation of extracellular amyloid β (Aβ) plaques and intracellular neurofibrillary tangles
of hyperphosphorylated tau protein. These markers correlate with the severity of clinical signs and symptoms
of the disease, and it is thought that they may be directly neurotoxic. However, a more recent paradigm is that
these aggregates of misfolded proteins may lead to a state of chronic neuroinflammation, and that this
inflammatory state is responsible for loss of neuronal function and neuron death. This inflammatory state is
achieved through activation of the innate microglia, as well as the relatively understudied (in this context)
activation of adaptive T lymphocytes. Regulatory T cells (Tregs) are a subset of T cells that dampen immune
responses and promote tissue repair after injury in various tissues including the brain. Recently, regulatory T
cells have been suggested to play an important role in AD. However, important gaps in our understanding
of Tregs in AD remain: What types of Tregs are found in the brain in AD mice relative to wildtype mice?
and, What role do Tregs play in the progression of AD? I will address this knowledge gap in two specific
aims. In Aim 1, I will characterize the types of Tregs and their spatial localization in the aging WT and AD
brains, while in Aim 2 I will establish the effect of increasing or decreasing Treg numbers or function. My
hypothesis is that brain-specific Tregs play a critical role in preventing or delaying AD progression, and that
increasing their number and function will lead to improved outcomes in AD. Successful completion of the aims
of this grant will provide insight into the role of Tregs in AD. These studies will enhance my training in
computational and hypothesis generating experiments (Aim 1), as well as hypothesis driven functional studies
(Aim 2).

## Key facts

- **NIH application ID:** 10824927
- **Project number:** 1F30AG085982-01
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Thomas R Hougard
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $53,974
- **Award type:** 1
- **Project period:** 2024-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10824927

## Citation

> US National Institutes of Health, RePORTER application 10824927, The Role of Regulatory T Cells in Alzheimer's Disease (1F30AG085982-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10824927. Licensed CC0.

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