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

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...

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Autores principales: Delgado-Peraza, Francheska, Nogueras-Ortiz, Carlos, Simonsen, Anja Hviid, Knight, De’Larrian DeAnté, Yao, Pamela J., Goetzl, Edward J., Jensen, Camilla Steen, Høgh, Peter, Gottrup, Hanne, Vestergaard, Karsten, Hasselbalch, Steen Gregers, Kapogiannis, Dimitrios
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10510190/
https://www.ncbi.nlm.nih.gov/pubmed/37730689
http://dx.doi.org/10.1186/s13195-023-01303-9
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author Delgado-Peraza, Francheska
Nogueras-Ortiz, Carlos
Simonsen, Anja Hviid
Knight, De’Larrian DeAnté
Yao, Pamela J.
Goetzl, Edward J.
Jensen, Camilla Steen
Høgh, Peter
Gottrup, Hanne
Vestergaard, Karsten
Hasselbalch, Steen Gregers
Kapogiannis, Dimitrios
author_facet Delgado-Peraza, Francheska
Nogueras-Ortiz, Carlos
Simonsen, Anja Hviid
Knight, De’Larrian DeAnté
Yao, Pamela J.
Goetzl, Edward J.
Jensen, Camilla Steen
Høgh, Peter
Gottrup, Hanne
Vestergaard, Karsten
Hasselbalch, Steen Gregers
Kapogiannis, Dimitrios
author_sort Delgado-Peraza, Francheska
collection PubMed
description 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: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13195-023-01303-9.
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spelling pubmed-105101902023-09-21 Neuron-derived extracellular vesicles in blood reveal effects of exercise in Alzheimer’s disease Delgado-Peraza, Francheska Nogueras-Ortiz, Carlos Simonsen, Anja Hviid Knight, De’Larrian DeAnté Yao, Pamela J. Goetzl, Edward J. Jensen, Camilla Steen Høgh, Peter Gottrup, Hanne Vestergaard, Karsten Hasselbalch, Steen Gregers Kapogiannis, Dimitrios Alzheimers Res Ther Research 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: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13195-023-01303-9. BioMed Central 2023-09-20 /pmc/articles/PMC10510190/ /pubmed/37730689 http://dx.doi.org/10.1186/s13195-023-01303-9 Text en © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Delgado-Peraza, Francheska
Nogueras-Ortiz, Carlos
Simonsen, Anja Hviid
Knight, De’Larrian DeAnté
Yao, Pamela J.
Goetzl, Edward J.
Jensen, Camilla Steen
Høgh, Peter
Gottrup, Hanne
Vestergaard, Karsten
Hasselbalch, Steen Gregers
Kapogiannis, Dimitrios
Neuron-derived extracellular vesicles in blood reveal effects of exercise in Alzheimer’s disease
title Neuron-derived extracellular vesicles in blood reveal effects of exercise in Alzheimer’s disease
title_full Neuron-derived extracellular vesicles in blood reveal effects of exercise in Alzheimer’s disease
title_fullStr Neuron-derived extracellular vesicles in blood reveal effects of exercise in Alzheimer’s disease
title_full_unstemmed Neuron-derived extracellular vesicles in blood reveal effects of exercise in Alzheimer’s disease
title_short Neuron-derived extracellular vesicles in blood reveal effects of exercise in Alzheimer’s disease
title_sort neuron-derived extracellular vesicles in blood reveal effects of exercise in alzheimer’s disease
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10510190/
https://www.ncbi.nlm.nih.gov/pubmed/37730689
http://dx.doi.org/10.1186/s13195-023-01303-9
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