Elevated peripheral inflammation is associated with choroid plexus enlargement in independent sporadic amyotrophic lateral sclerosis cohorts.

IF 5.9 1区医学 Q1 NEUROSCIENCES

Fluids and Barriers of the CNS Pub Date : 2024-10-21 DOI:10.1186/s12987-024-00586-w

Sujuan Sun, Yujing Chen, Yan Yun, Bing Zhao, Qingguo Ren, Xiaohan Sun, Xiangshui Meng, Chuanzhu Yan, Pengfei Lin, Shuangwu Liu

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引用次数: 0

Abstract

Background: Using neuroimaging techniques, growing evidence has suggested that the choroid plexus (CP) volume is enlarged in multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Notably, the CP has been suggested to play an important role in inflammation-induced CNS damage under disease conditions. However, to our knowledge, no study has investigated the relationships between peripheral inflammation and CP volume in sporadic ALS patients. Thus, in this study, we aimed to verify CP enlargement and explore its association with peripheral inflammation in vivo in independent ALS cohorts.

Methods: Based on structural MRI data, CP volume was measured using Gaussian mixture models and further manually corrected in two independent cohorts of sporadic ALS patients and healthy controls (HCs). Serum inflammatory protein levels were measured using a novel high-sensitivity Olink proximity extension assay (PEA) technique. Xtreme gradient boosting (XGBoost) was used to explore the contribution of peripheral inflammatory factors to CP enlargement. Then, partial correlation analyses were performed.

Results: CP volumes were significantly higher in ALS patients than in HCs in the independent cohorts. Compared with HCs, serum levels of CRP, IL-6, CXCL10, and 35 other inflammatory factors were significantly increased in ALS patients. Using the XGBoost approach, we established a model-based importance of features, and the top three predictors of CP volume in ALS patients were CRP, IL-6, and CXCL10 (with gains of 0.24, 0.18, and 0.15, respectively). Correlation analyses revealed that CRP, IL-6, and CXCL10 were significantly associated with CP volume in ALS patients (r = 0.462 ∼ 0.636, p < 0.001).

Conclusion: Our study is the first to reveal a consistent and replicable contribution of peripheral inflammation to CP enlargement in vivo in sporadic ALS patients. Given that CP enlargement has been recently detected in other brain diseases, these findings should consider extending to other disease conditions with a peripheral inflammatory component.

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在独立的散发性肌萎缩侧索硬化症队列中，外周炎症升高与脉络丛扩大有关。

背景：越来越多的证据表明，利用神经影像学技术，脉络丛（CP）的体积在包括肌萎缩侧索硬化症（ALS）在内的多种神经退行性疾病中会增大。值得注意的是，在疾病条件下，脉络丛被认为在炎症诱发的中枢神经系统损伤中扮演着重要角色。然而，据我们所知，还没有研究调查过散发性 ALS 患者外周炎症与 CP 体积之间的关系。因此，在本研究中，我们的目的是在独立的 ALS 队列中验证 CP 的增大，并探讨其与体内外周炎症的关系：方法：基于结构性核磁共振成像数据，使用高斯混合模型测量 CP 体积，并进一步在两个独立的散发性 ALS 患者队列和健康对照组（HCs）中进行人工校正。血清炎症蛋白水平采用新型高灵敏度Olink近距离延伸测定（PEA）技术进行测量。使用Xtreme梯度增强（XGBoost）技术探讨了外周炎症因子对CP增大的贡献。然后进行了偏相关分析：结果：在独立队列中，ALS 患者的 CP 体积明显高于 HCs。与 HCs 相比，ALS 患者血清中 CRP、IL-6、CXCL10 和其他 35 种炎症因子水平明显升高。利用 XGBoost 方法，我们建立了基于模型的特征重要性，ALS 患者 CP 容量的前三位预测因子是 CRP、IL-6 和 CXCL10（增益分别为 0.24、0.18 和 0.15）。相关性分析表明，CRP、IL-6 和 CXCL10 与 ALS 患者的 CP 容量显著相关（r = 0.462 ∼ 0.636，p 结论：我们的研究首次揭示了 ALS 患者的 CP 容量与 CRP、IL-6 和 CXCL10 的相关性：我们的研究首次揭示了在散发性 ALS 患者体内，外周炎症对 CP 增大具有一致且可复制的作用。鉴于最近在其他脑部疾病中也发现了 CP 扩大，这些发现应考虑扩展到其他具有外周炎症成分的疾病。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Fluids and Barriers of the CNS Neuroscience-Developmental Neuroscience

CiteScore

10.70

自引率

8.20%

发文量

审稿时长

14 weeks

期刊介绍： "Fluids and Barriers of the CNS" is a scholarly open access journal that specializes in the intricate world of the central nervous system's fluids and barriers, which are pivotal for the health and well-being of the human body. This journal is a peer-reviewed platform that welcomes research manuscripts exploring the full spectrum of CNS fluids and barriers, with a particular focus on their roles in both health and disease. At the heart of this journal's interest is the cerebrospinal fluid (CSF), a vital fluid that circulates within the brain and spinal cord, playing a multifaceted role in the normal functioning of the brain and in various neurological conditions. The journal delves into the composition, circulation, and absorption of CSF, as well as its relationship with the parenchymal interstitial fluid and the neurovascular unit at the blood-brain barrier (BBB).