TY - JOUR

T1 - Neuron-derived extracellular vesicles in blood reveal effects of exercise in Alzheimer’s disease

AU - Delgado-Peraza, Francheska

AU - Nogueras-Ortiz, Carlos

AU - Simonsen, Anja Hviid

AU - Knight, De’Larrian De Anté

AU - Yao, Pamela J.

AU - Goetzl, Edward J.

AU - Jensen, Camilla Steen

AU - Høgh, Peter

AU - Gottrup, Hanne

AU - Vestergaard, Karsten

AU - Hasselbalch, Steen Gregers

AU - Kapogiannis, Dimitrios

N1 - Publisher Copyright: © 2023, BioMed Central Ltd., part of Springer Nature.

PY - 2023

Y1 - 2023

N2 - 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: [Figure not available: see fulltext.].

AB - 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: [Figure not available: see fulltext.].

KW - ADEX

KW - Alzheimer’s disease

KW - APOE

KW - BDNF

KW - Biomarkers

KW - Exercise

KW - Exerkines

KW - Extracellular vesicles

KW - Humanin

KW - proBDNF

U2 - 10.1186/s13195-023-01303-9

DO - 10.1186/s13195-023-01303-9

M3 - Journal article

C2 - 37730689

AN - SCOPUS:85171809476

VL - 15

JO - Alzheimer's Research and Therapy

JF - Alzheimer's Research and Therapy

SN - 1758-9193

IS - 1

M1 - 156

ER -