# Immunomodulatory and behavioral effects of CAR T regulatory cell therapy for Alzheimer's Disease”.

> **NIH NIH R21** · DARTMOUTH COLLEGE · 2024 · $205,000

## Abstract

Project Summary/Abstract:
Alzheimer’s disease (AD) is a progressive neurodegenerative disease that is one of the primary reasons for
memory dysfunction and dementia after 60 years of age. Neuronal dysfunction and death in the frontal cortex
and hippocampus, along with glia-mediated neuroinflammation and formation of aberrant protein aggregates
and fibrils are hallmarks of AD. Sporadic and familial forms of AD have an overproduction and/or decreased
clearance of extracellular amyloid-beta (Aβ) peptides and intraneuronal tangles of twisted tau protein fibers.
Neuroinflammation is known to occur in AD, and when associated near Aβ plaques there is a greater
neurodegeneration. Furthermore, peripheral immune activity and inflammation can affect inflammation in the
CNS. T regulatory cells (Tregs) are a subset of T cells that have inherent anti-inflammatory and
immunomodulatory properties. Tregs are found in the CNS under steady state conditions and increase trafficking
to regions of CNS inflammation. Less active or decreased numbers of Tregs has been found in AD patients and
depletion of Tregs can accelerate cognitive defects in murine AD models. We hypothesize that Tregs expressing
chimeric antigen receptors (CARs) with specificity to amyloid-beta (Aβ) will have immunomodulatory activity and
improve cognitive function of the 5xFAD B6 mice, a murine AD model. The aim of this proposal is to test the
innovative concept that Tregs engineered to express CARs against amyloid-beta will demonstrate
immunomodulatory effects in the CNS and in the peripheral tissues resulting in improved cognitive behavior. The
data generated will provide key proof-of-concept data to develop this novel therapeutic idea forward.

## Key facts

- **NIH application ID:** 10825551
- **Project number:** 5R21AG081632-02
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Charles L. Sentman
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $205,000
- **Award type:** 5
- **Project period:** 2023-04-15 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10825551

## Citation

> US National Institutes of Health, RePORTER application 10825551, Immunomodulatory and behavioral effects of CAR T regulatory cell therapy for Alzheimer's Disease”. (5R21AG081632-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10825551. Licensed CC0.

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