# HDAC9, Aging and Alzheimer's Disease

> **NIH NIH R56** · AUGUSTA UNIVERSITY · 2020 · $762,845

## Abstract

PROJECT SUMMARY
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, accounting for 60–80 % of dementia
cases. Aging is the leading risk factor for AD; however, the mechanisms linking aging to the pathogenesis of AD
remain elusive. Aging exerts profound impacts on peripheral tissues and brain. The dysfunctional crosstalk
between peripheral systems and brain during aging may play a role in the pathogenesis and progression of AD.
Advancing age induces adipose tissue dysfunction that drives metabolic decline and systemic inflammation and
causes dysregulated production of neuroprotective adipokines and proinflammatory cytokines, which may
accelerate brain aging and the onset or progression of AD. We found that aging increases expression of histone
deacetylase 9 (HDAC9), an endogenous repressor of adipogenic differentiation, in human and mouse adipose
tissue, but decreases HDAC9 expression in the brain. Our findings suggest that HDAC9 in adipose tissue and
brain has distinct roles in mediating aging-related effects. We propose to determine 1) the impact of adipocyte
HDAC9 on aging- and AD-related metabolic and inflammatory profiles, neuropathology and cognitive impairment;
2) the functional role of HDAC9 in hippocampal and cortical neurons in age- and AD-related neuropathological
and cognitive phenotypes; and 3) the mechanisms underlying age- and AD-associated changes in HDAC9 gene
expression in adipose tissue and brain.

## Key facts

- **NIH application ID:** 10017152
- **Project number:** 5R56AG064895-02
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** Xin-Yun Lu
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $762,845
- **Award type:** 5
- **Project period:** 2019-09-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10017152

## Citation

> US National Institutes of Health, RePORTER application 10017152, HDAC9, Aging and Alzheimer's Disease (5R56AG064895-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10017152. Licensed CC0.

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