# Senescence-Induced Progression of Alzheimer's Disease

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2020 · $376,250

## Abstract

Project Description
Alzheimer's disease (AD) is an age-related neurodegenerative disorder featuring progressive cognitive,
functional, and behavioral defects. Currently, more than 5.6 million Americans suffer from AD, and this number
is projected to increase to 15.0 million by 2060. Despite several clinical interventions have been approved for
treatment of AD, unfortunately they have demonstrated only modest effects in modifying the clinical symptoms
for relatively short periods with none showing a clear therapeutic effect on disease progression. The lack of a
clear understanding of the mechanisms driving the pathogenesis and progression of AD is a significant barrier
to the development of innovative and effective therapies. The goal of this proposal is to address this gap by
defining the role of senescence in brain aging and AD pathogenesis. My lab and those of others have shown
that the number of senescent cells was markedly increased in the brain of AD patients and that the removal of
senescent cells can prevent cognitive declines and attenuate AD pathology in preclinical animal models. These
results suggest a critical role for senescent cells in AD pathogenesis and treatment. Based on evidence
provided by us and others that 1) oxidative stress is a pathological feature of AD, and 2) increased numbers of
senescent astrocytes have been identified in the brain of AD patients, we hypothesize that aging-associated
oxidative stress leads to the accumulation of senescent cells in the brain, which in turn promote the
pathogenesis and progression of AD via exacerbating amyloid beta (Aβ)-induced neurotoxicity and tau
pathology. Therefore, pharmacological elimination of senescent cells can be exploited as a new strategy for
AD prevention and treatment. There Specific Aims are proposed to test this hypothesis: in Aim 1 we will
determine if there is greater cell type-specific senescence burden in AD as compared to healthy aging brains,
in Aim 2 we will elucidate the mechanisms by which senescent cells influence AD pathogenesis and
progression, and in Aim 3 we will evaluate the therapeutic potential of selective senolytic agents to prevent and
mitigate AD progression and cognitive declines. Successful completion of this project will provide novel insights
into the mechanisms by which senescent cells affect brain aging and drive the pathogenesis of AD. More
importantly, we anticipate that outcomes of this study will substantially facilitate the development of new and
more efficacious strategies for AD prevention and treatment.

## Key facts

- **NIH application ID:** 10044094
- **Project number:** 1R01AG068286-01
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Gavin Yong Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $376,250
- **Award type:** 1
- **Project period:** 2020-09-15 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10044094

## Citation

> US National Institutes of Health, RePORTER application 10044094, Senescence-Induced Progression of Alzheimer's Disease (1R01AG068286-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10044094. Licensed CC0.

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