# Targeting P21-Highly-Expressing Senescent Cells In Vivo for Improving Cognitive Function in the Alzheimers Diseases

> **NIH NIH R03** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2021 · $164,000

## Abstract

Project Summary
Alzheimer's disease (AD) is the most common age-dependent neurodegenerative disease. Currently, no
disease-modifying therapy is available to treat AD effectively in clinic. New therapeutic targets are desired for
AD treatment and prevention. Delaying the fundamental aging process might simultaneously alleviate a range
of age-related diseases, including AD. The accumulation of senescent cells in various tissues is one of the
most prominent features of aging. Clearance of senescent cells can slow down biological aging process and
various clinically-relevant consequences. However, the role and underlying mechanisms of senescent cells in
AD is not fully understood. To examine the relationship between senescent cells and AD, we have generated
and validated a novel “p21-Cre” transgenic mouse model containing a p21 (a key marker for cellular
senescence) promoter driving a Cre fused to a tamoxifen-inducible estrogen receptor (ER) element. This novel
model enables us to monitor, kill or modulate p21-highly-expressing (p21high) cells in vivo without affecting
other cells. In our preliminary studies, we find that p21high cells accumulate in AD brains. In this study, we will
test our central hypothesis that targeting p21high cells will alleviate AD and cognitive dysfunction. We will use
p21-Cre mouse models to examine the role of p21high cells in AD. This project will have a broad impact on both
aging and AD research by determining how p21high cells contribute to AD. Using multiple in vivo models, we
expect to gain a comprehensive understanding of p21high cells in AD in vivo. Results from this work will also
enable future testing of pharmacological interventions that eliminate these cells to treat not only AD, but also a
wide range of age-related diseases.

## Key facts

- **NIH application ID:** 10196320
- **Project number:** 1R03AG072374-01
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Ming Xu
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $164,000
- **Award type:** 1
- **Project period:** 2021-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10196320

## Citation

> US National Institutes of Health, RePORTER application 10196320, Targeting P21-Highly-Expressing Senescent Cells In Vivo for Improving Cognitive Function in the Alzheimers Diseases (1R03AG072374-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10196320. Licensed CC0.

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