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Neuron-derived extracellular vesicles in blood reveal effects of exercise in Alzheimer's disease
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This human trial examined blood neuron-derived extracellular vesicles (NDEVs) from 95 participants with mild to moderate Alzheimer's disease enrolled in the ADEX exercise study, randomized to exercise or control groups and sampled at baseline and 16 weeks. NDEV levels of proBDNF, BDNF, and humanin increased in the exercise group, particularly among APOE ε4 carriers, while remaining unchanged in controls. Correlations among these biomarkers seen at baseline persisted after exercise, and NDEV levels of other exercise-responsive proteins (exerkines) did not change. The authors suggest neuroprotective factors in NDEVs may be linked to exercise-related cognitive changes and that APOE ε4 carriers may respond differently to physical activity, while unchanged exerkine levels suggest exercise affects neurons and peripheral tissues through separate pathways.
Abstract
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. 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. 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. 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. The Effect of Physical Exercise in Alzheimer Patients (ADEX) was registered in ClinicalTrials.gov on April 30, 2012 with the identifier NCT01681602.
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