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Alzheimer's Research & Therapy
Published in: Alzheimer's Research & Therapy 1/2023

Open Access 01-12-2023 | Alzheimer's Disease | Research

Neuron-derived extracellular vesicles in blood reveal effects of exercise in Alzheimer’s disease

Authors: Francheska Delgado-Peraza, Carlos Nogueras-Ortiz, Anja Hviid Simonsen, De’Larrian DeAnté Knight, Pamela J. Yao, Edward J. Goetzl, Camilla Steen Jensen, Peter Høgh, Hanne Gottrup, Karsten Vestergaard, Steen Gregers Hasselbalch, Dimitrios Kapogiannis

Published in: Alzheimer's Research & Therapy | Issue 1/2023

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Abstract

Background

Neuron-derived extracellular vesicles (NDEVs) in blood may be used to derive biomarkers for the effects of exercise in Alzheimer’s disease (AD). For this purpose, we studied changes in neuroprotective proteins proBDNF, BDNF, and humanin in plasma NDEVs from patients with mild to moderate AD participating in the randomized controlled trial (RCT) of exercise ADEX.

Methods

proBDNF, BDNF, and humanin were quantified in NDEVs immunocaptured from the plasma of 95 ADEX participants, randomized into exercise and control groups, and collected at baseline and 16 weeks. Exploratorily, we also quantified NDEV levels of putative exerkines known to respond to exercise in peripheral tissues.

Results

NDEV levels of proBDNF, BDNF, and humanin increased in the exercise group, especially in APOE ε4 carriers, but remained unchanged in the control group. Inter-correlations between NDEV biomarkers observed at baseline were maintained after exercise. NDEV levels of putative exerkines remained unchanged.

Conclusions

Findings suggest that the cognitive benefits of exercise could be mediated by the upregulation of neuroprotective factors in NDEVs. Additionally, our results indicate that AD subjects carrying APOE ε4 are more responsive to the neuroprotective effects of physical activity. Unchanged NDEV levels of putative exerkines after physical activity imply that exercise engages different pathways in neurons and peripheral tissues. Future studies should aim to expand upon the effects of exercise duration, intensity, and type in NDEVs from patients with early AD and additional neurodegenerative disorders.

Trial registration

The Effect of Physical Exercise in Alzheimer Patients (ADEX) was registered in ClinicalTrials.gov on April 30, 2012 with the identifier NCT01681602.

Graphical abstract

Appendix
Available only for authorised users
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Metadata
Title
Neuron-derived extracellular vesicles in blood reveal effects of exercise in Alzheimer’s disease
Authors
Francheska Delgado-Peraza
Carlos Nogueras-Ortiz
Anja Hviid Simonsen
De’Larrian DeAnté Knight
Pamela J. Yao
Edward J. Goetzl
Camilla Steen Jensen
Peter Høgh
Hanne Gottrup
Karsten Vestergaard
Steen Gregers Hasselbalch
Dimitrios Kapogiannis
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2023
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-023-01303-9

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