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

Content Provider	Springer Nature : BioMed Central
Author	Sun, Sujuan Chen, Yujing Yun, Yan Zhao, Bing Ren, Qingguo Sun, Xiaohan Meng, Xiangshui Yan, Chuanzhu Lin, Pengfei Liu, Shuangwu
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.
Related Links	https://fluidsbarrierscns.biomedcentral.com/counter/pdf/10.1186/s12987-024-00586-w.pdf
Ending Page	10
Page Count	10
Starting Page	1
File Format	HTM / HTML
ISSN	20458118
DOI	10.1186/s12987-024-00586-w
Journal	Fluids and Barriers of the CNS
Issue Number	1
Volume Number	21
Language	English
Publisher	BioMed Central
Publisher Date	2024-10-21
Access Restriction	Open
Subject Keyword	Neurosciences Hematology Neurobiology ALS Choroid plexus MRI Inflammation
Content Type	Text
Resource Type	Article
Subject	Neurology Developmental Neuroscience Medicine Cellular and Molecular Neuroscience
Journal Impact Factor	5.9/2023
5-Year Journal Impact Factor	7.5/2023

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