运动作为阿尔茨海默病患者脑脊液和血浆中炎症的潜在调节剂。

Exercise as a potential modulator of inflammation in patients with Alzheimer's disease measured in cerebrospinal fluid and plasma.

机构信息

Danish Dementia Research Centre, Department of Neurology, Rigshospitalet University of Copenhagen, DK-2100 Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Denmark.

Department of Bioanalysis, Lundbeck, 2500 Valby, Denmark.

出版信息

Exp Gerontol. 2019 Jul 1;121:91-98. doi: 10.1016/j.exger.2019.04.003. Epub 2019 Apr 11.

DOI:10.1016/j.exger.2019.04.003

PMID:30980923

Abstract

BACKGROUND

Neuroinflammation is recognized as part of the pathological progression of Alzheimer's disease (AD), but the molecular mechanisms are still not entirely clear. Systemically, physical exercise has shown to have a positive modulating effect on markers of inflammation. It is not known if this general effect also takes place in the central nervous system in AD. The aim of this study was to investigate the effect of 16 weeks of moderate to high-intensity physical exercise on selected biomarkers of inflammation both systemically and in the CNS, in patients with AD.

METHODS

Plasma and cerebrospinal fluid (CSF) from 198 patients with Alzheimer's disease participating in the Preserving Cognition, Quality of Life, Physical Health and Functional Ability in Alzheimer's Disease: The Effect of Physical Exercise (ADEX) study were analyzed for concentrations of 8‑isoprostane, soluble trigger receptor expressed on myeloid cells 2 (sTREM2), and the MSD v-plex proinflammation panel 1 human containing interferon gamma (IFNγ), Interleukin-10 (IL10), IL12p70, IL13, IL1β, IL2, IL4, IL6, IL8, and tumor necrosis factor alpha (TNFα), before and after a 16-week intervention with physical exercise, and we studied whether changes were modulated by the patients' APOE genotype.

RESULTS

Most inflammatory markers remained unchanged after exercise. We found an increasing effect of 16 weeks of physical exercise on sTREM2 measured in CSF. Further, IL6 in plasma increased in the exercise group after physical exercise (mean relative change 41.03, SD 76.7), compared to controls (-0.97, SD 49.4). In a sub-analysis according to APOE genotype, we found that in ε4 carriers, exercise had a stabilizing effect on IFNγ concentration with a mean relative change of 7.84 (SD 42.6), as compared to controls (114.7 (SD 188.3), p = 0.038.

CONCLUSION

Our findings indicate an effect of physical exercise on markers of neuroinflammation in CSF measured by an increase in sTREM2 in patients with AD. Further, there may be a small inflammatory systemic effect related to physical exercise in patients with AD.

摘要

背景

神经炎症被认为是阿尔茨海默病（AD）病理进展的一部分，但分子机制仍不完全清楚。在系统层面上，运动已被证明对炎症标志物具有积极的调节作用。目前尚不清楚这种一般效应是否也会发生在 AD 的中枢神经系统中。本研究旨在探讨 16 周中等至高强度的身体锻炼对 AD 患者系统性和中枢神经系统中选定的炎症生物标志物的影响。

方法

对参与保护认知、生活质量、身体健康和阿尔茨海默病功能能力：身体锻炼的影响（ADEX）研究的 198 名 AD 患者的血浆和脑脊液（CSF）进行分析，以检测 8-异前列腺素、可溶性髓样细胞触发受体 2（sTREM2）以及 MSD v-plex proinflammation 面板 1 人类干扰素 γ（IFNγ）、白细胞介素 10（IL10）、白细胞介素 12p70、白细胞介素 13、白细胞介素 1β、白细胞介素 2、白细胞介素 4、白细胞介素 6、白细胞介素 8 和肿瘤坏死因子 α（TNFα）的浓度，在 16 周的身体锻炼干预前后，并研究这些变化是否受患者 APOE 基因型的调节。

结果

运动后大多数炎症标志物保持不变。我们发现，16 周的身体锻炼对 CSF 中 sTREM2 的测量有增加的效果。此外，运动组的血浆中 IL6 在运动后增加（相对变化 41.03，SD 76.7），而对照组则减少（-0.97，SD 49.4）。在根据 APOE 基因型进行的亚分析中，我们发现，在 ε4 携带者中，运动对 IFNγ 浓度具有稳定作用，相对变化为 7.84（SD 42.6），而对照组为 114.7（SD 188.3），p=0.038。