# Muscle weakness and neurogeneration; exercise as a therapeutic approach

> **NIH NIH U01** · UNIVERSITY OF FLORIDA · 2021 · $374,250

## Abstract

Abstract: This administrative supplement is submitted in response to Notice Number: NOT-AG-20-034:
Alzheimer's Disease Administrative supplements for NIH grants. This supplement outlines experiments to
extend the parent U01 (UF PASS: Regulation of exercise transducers) to pursue the interaction between
exercise, skeletal muscle health and progression of pathology in a mouse model of Alzheimer’s disease (AD).
The parent award is part of the MoTrPAC consortium that combines well defined exercise interventions with
multi-omics analysis to develop a map of molecular transducers that link exercise to systemic health. For this
administrative supplement we will use a defined mouse model of AD with a treadmill training protocol based on
the protocol used for MoTrPAC. We will also be in a position to analyze our outcomes data in the context of the
larger multiomics data available from MoTrPAC to expand our understanding of potential cross tissue
interpretations.
A major challenge in the field of Alzheimer’s disease (AD) is the poor understanding of how tau pathology
promotes disease. Consequently, therapeutic interventions are ineffective and clinical trials for AD have failed.
The working model for this supplement is that exercise mitigates the onset and progression of AD tau
pathology through impacting skeletal muscle health as well as direct effects on the brain. The rationale for this
model comes from two complementary but not fully explored sub-fields: “AD and muscle/sarcopenia” and “AD
and exercise”. Several clinical studies have reported that muscle weakness and loss of muscle mass occurs at
a faster rate in AD patients. These muscle changes in the patients are also associated with brain atrophy and
diminished cognitive performance. In addition, several studies using animal models of AD have demonstrated
changes in skeletal muscle metabolism at times prior to the appearance of AD pathology in the brain. These
observations are consistent with our preliminary data that found significant muscle weakness in a tauopathy
mouse model of AD prior to overt signs of neurodegeneration. There are also a large number of clinical and
preclinical studies showing that exercise training, primarily endurance exercise, has a positive impact on the
onset and progression of AD. Thus, we propose to integrate the concepts of exercise, muscle health and brain
health to define molecules and pathways that attenuate the onset and progression of AD tau pathology in the
brain. We propose the following Specific Aims.
Aim 1) To determine the molecular, histological and phenotypic changes in skeletal muscle and brain
in an acquired tauopathy model of AD in mice.
Aim 2) To use a running exercise intervention with the AD-tauopathy mouse model to identify
molecular sites through which tau pathology is attenuated.

## Key facts

- **NIH application ID:** 10287587
- **Project number:** 3U01AG055137-05S1
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Karyn A Esser
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $374,250
- **Award type:** 3
- **Project period:** 2016-12-15 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10287587

## Citation

> US National Institutes of Health, RePORTER application 10287587, Muscle weakness and neurogeneration; exercise as a therapeutic approach (3U01AG055137-05S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10287587. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*