# Resistance exercise to mitigate glucocorticoid myopathy during Alzheimer’s

> **NIH NIH R03** · FLORIDA STATE UNIVERSITY · 2024 · $74,332

## Abstract

Project Summary/Abstract
Healthy skeletal muscle slows cognitive decline in Alzheimer’s patients. The 3-fold increase in glucocorticoid
production that occurs in Alzheimer’s patients renders their skeletal muscle vulnerable to glucocorticoid-
induced myopathy, which is the most common, toxic, non-inflammatory muscle disease in those with elevated
glucocorticoids. While this myopathy would decrease muscle health and augment cognitive decline, there are
no ways to prevent glucocorticoid myopathy in this population. The inability to treat glucocorticoid myopathy in
Alzheimer’s patients limits a clinician’s ability to preserve cognitive function. Despite this issue, our new data
show that resistance exercise may be an immediate way for Alzheimer’s patients to blunt the signals that
initiate glucocorticoid myopathy. Specifically, our laboratory’s recent publication in healthy muscle shows that a
bout of resistance exercise reduces nuclear translocation of the glucocorticoid receptor, a critical step in the
process by which glucocorticoids initiate myopathy. The glucocorticoid receptor initiates the myopathy in large
part by changing the muscle transcriptome. Accordingly, our new preliminary data show that a bout of
resistance exercise will also reverse the glucocorticoid-mediated induction of some glucocorticoid target genes.
While promising as a therapy, Alzheimer’s disease induces a novel muscle pathology characterized by
accumulation of amyloid-beta plaques that compromises skeletal muscle function, which could render
resistance exercise less- or ineffective at mitigating the signals that initiate glucocorticoid myopathy. Therefore,
the objective of this proposal is to test whether Alzheimer’s skeletal muscle disease pathology affects the
ability of resistance exercise to mitigate the signals that initiate glucocorticoid myopathy. Aim 1 will define the
impact of Alzheimer’s muscle disease pathology on the ability of resistance exercise to reduce glucocorticoid
receptor activation in the skeletal muscle. Aim 2 will classify and characterize the glucocorticoid target genes
in healthy muscle and muscle with Alzheimer’s disease pathology based upon how their hormone-regulated
gene expression responds to a bout of resistance exercise. In all, this pilot study will define the extent to which
resistance exercise can blunt the signals that initiate glucocorticoid myopathy in the presence of Alzheimer’s
muscle pathology. These outcomes are significant because they will provide key information for clinicians to
effectively use resistance exercise as part of a comprehensive strategy to prevent glucocorticoid myopathy and
preserve cognitive function in the Alzheimer’s population.

## Key facts

- **NIH application ID:** 10808941
- **Project number:** 5R03AG078886-02
- **Recipient organization:** FLORIDA STATE UNIVERSITY
- **Principal Investigator:** Bradley S Gordon
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $74,332
- **Award type:** 5
- **Project period:** 2023-03-15 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10808941

## Citation

> US National Institutes of Health, RePORTER application 10808941, Resistance exercise to mitigate glucocorticoid myopathy during Alzheimer’s (5R03AG078886-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10808941. Licensed CC0.

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