# Chimeric antigen receptor T regulatory cells as therapy for Alzheimer's Disease

> **NIH NIH R21** · DARTMOUTH COLLEGE · 2020 · $451,000

## 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 microglia-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. Data suggest that inflammatory microglia, the resident macrophages of the central nervous
system, have a role in neurodegeneration and cognitive decline. 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) would have therapeutic immunomodulatory and localized disease-modifying activity at brain
regions of Aβ accumulation and progressive neurodegeneration. The aim of this proposal is to test the innovative
concept that Tregs engineered to express CARs against Aβ will demonstrate immunoregulatory and
neuroprotective activities in mouse models of Alzheimer's disease. We will test murine and human Tregs for
activity in AD models when Aβ is present. The data generated will provide key proof-of-concept data to move
this novel therapeutic idea forward

## Key facts

- **NIH application ID:** 10025408
- **Project number:** 1R21AG067971-01
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Charles L. Sentman
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $451,000
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10025408

## Citation

> US National Institutes of Health, RePORTER application 10025408, Chimeric antigen receptor T regulatory cells as therapy for Alzheimer's Disease (1R21AG067971-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10025408. Licensed CC0.

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