Laboratory of Clinical Investigation, Intramural Research Program, National Institute On Aging, National Institutes of Health, Baltimore, MD, 21224, USA.
Danish Dementia Research Centre, Copenhagen University Hospital - Rigshospitalet, 2100, Copenhagen, Denmark.
Alzheimers Res Ther. 2023 Sep 20;15(1):156. doi: 10.1186/s13195-023-01303-9.
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.
血液中的神经元衍生细胞外囊泡（NDEVs）可用于衍生阿尔茨海默病（AD）中运动影响的生物标志物。为此，我们研究了轻度至中度 AD 患者参加运动 ADEX 随机对照试验（RCT）时血浆 NDEVs 中神经保护蛋白 proBDNF、BDNF 和 humanin 的变化。
从 95 名 ADEX 参与者的血浆中免疫捕获 NDEVs，对其进行定量分析，参与者被随机分为运动组和对照组，并在基线和 16 周时进行采集。探索性地，我们还定量分析了已知对周围组织中运动有反应的潜在外泌体的 NDEV 水平。
运动组 NDEVs 的 proBDNF、BDNF 和 humanin 水平增加，尤其是 APOE ε4 携带者，但对照组无变化。运动后观察到的 NDEV 生物标志物之间的相关性仍然存在。潜在外泌体的 NDEV 水平保持不变。
研究结果表明，运动的认知益处可能是通过 NDEVs 中神经保护因子的上调介导的。此外，我们的结果表明，携带 APOE ε4 的 AD 患者对身体活动的神经保护作用更为敏感。运动后潜在外泌体的 NDEV 水平不变，这意味着运动在神经元和周围组织中涉及不同的途径。未来的研究应旨在扩展早期 AD 和其他神经退行性疾病患者 NDEVs 中运动持续时间、强度和类型的影响。
2012 年 4 月 30 日，在 ClinicalTrials.gov 上注册了《阿尔茨海默病患者的体育锻炼效果》（ADEX），标识符为 NCT01681602。
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