# Skeletal muscle extracellular vesicle signaling in Alzheimer's Disease prevention

> **NIH NIH R21** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2020 · $420,750

## Abstract

ABSTRACT
Alzheimer's Disease (AD) represents a devastating disease characterized by the presence of protein
aggregates within the brain that are closely linked to synaptic nerve loss and progressive cognitive deficits. A
lifestyle intervention, such as exercise, can improve cognitive function in AD patients. While the mechanisms
that mediate this change are likely multifactorial, our proposal investigates the potential for a novel cell-to-cell
signaling mechanism via transfer of extracellular vesicles (EV; exosomes and microvesicles) to mediate
changes in the neuronal cells. Our preliminary data show that aerobic exercise can both increase the number
of EVs in serum as well as their content of heat shock proteins (HSP). Moreover, we demonstrate that EVs
with elevated HSP can inhibit protein aggregation within neuronal cells. We provide additional evidence
suggesting this EV clearance uses an autophagosomal pathway. Our central hypothesis is exercise
induced EVs can impede the protein aggregation typically associated with AD. In this proposal we will
test this in two independent specific aims. Aim 1 will assess whether exercise of AD patients modulates EV
content, numbers and function (i.e., ability to block protein aggregation). Aim 2 will assess the molecular
underpinning through which exercise- induced EVs and their associated HSPs might be working. In this latter
aim, we will test whether the autophagosomal pathway is involved in the removal of amyloid-β-peptide (Aβ)
containing protein aggregates. This proposal represents an innovative approach to study AD, and has the
potential to provide insight into how exercise can improve AD outcomes and ultimately may provide novel
therapeutic approaches.

## Key facts

- **NIH application ID:** 9917535
- **Project number:** 1R21AG066488-01
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** LANE K. CHRISTENSON
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $420,750
- **Award type:** 1
- **Project period:** 2020-01-15 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9917535

## Citation

> US National Institutes of Health, RePORTER application 9917535, Skeletal muscle extracellular vesicle signaling in Alzheimer's Disease prevention (1R21AG066488-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9917535. Licensed CC0.

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