神经系统疾病中脑脊液和血清代谢组的综合分析。

Comprehensive analysis of the cerebrospinal fluid and serum metabolome in neurological diseases.

机构信息

Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Charitéplatz 1, 10117, Berlin, Germany.

Berlin Institute of Health at Charité, Charité - Universitätsmedizin Berlin, Berlin, Germany.

出版信息

J Neuroinflammation. 2024 Sep 26;21(1):234. doi: 10.1186/s12974-024-03218-0.

DOI:10.1186/s12974-024-03218-0

PMID:39327581

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11430517/

Abstract

BACKGROUND

Comprehensive characterization of the metabolome in cerebrospinal fluid (CSF) and serum by Nuclear Magnetic Resonance (NMR) spectroscopy may identify biomarkers and contribute to the understanding of the pathophysiology of neurological diseases.

METHODS

Metabolites were determined by NMR spectroscopy in stored CSF/serum samples of 20 patients with Parkinson's disease, 25 patients with other neuro-degenerative diseases, 22 patients with cerebral ischemia, 48 patients with multiple sclerosis, and 58 control patients with normal CSF findings. The data set was analysed using descriptive and multivariate statistics, as well as machine learning models.

RESULTS

CSF glucose and lactic acid measured by NMR spectroscopy and routine clinical chemistry showed a strong correlation between both methods (glucose, R = 0.87, n = 173; lactic acid, R = 0.74, n = 173). NMR spectroscopy detected a total of 99 metabolites; 51 in both, CSF and serum, 16 in CSF only, and 32 in serum only. CSF concentrations of some metabolites increased with age and/or decreasing blood-brain-barrier function. Metabolite detection rates were overall similar among the different disease groups. However, in two-group comparisons, absolute metabolite levels in CSF and serum discriminated between multiple sclerosis and neurodegenerative diseases (area under the curve (AUC) = 0.96), multiple sclerosis and Parkinson's disease (AUC = 0.89), and Parkinson's disease and control patients (AUC = 0.91), as demonstrated by random forest statistical models. Orthogonal partial least square discriminant analysis using absolute metabolite levels in CSF and serum furthermore permitted separation of Parkinson's disease and neurodegenerative diseases. CSF propionic acid levels were about fourfold lower in Parkinson's disease as compared to neurodegenerative diseases.

CONCLUSIONS

These findings outline the landscape of the CSF and serum metabolome in different categories of neurological diseases and identify age and blood-brain-barrier function as relevant co-factors for CSF levels of certain metabolites. Metabolome profiles as determined by NMR spectroscopy may potentially aid in differentiating groups of patients with different neurological diseases, including clinically meaningful differentiations, such as Parkinson's disease from other neurodegenerative diseases.

摘要

背景

通过核磁共振（NMR）光谱对脑脊液（CSF）和血清中的代谢组进行全面描述，可能有助于发现生物标志物，并有助于理解神经疾病的病理生理学。

方法

通过 NMR 光谱法测定 20 例帕金森病患者、25 例其他神经退行性疾病患者、22 例脑缺血患者、48 例多发性硬化症患者及 58 例 CSF 正常的对照组患者储存的 CSF/血清样本中的代谢物。使用描述性和多变量统计以及机器学习模型对数据集进行分析。

结果

通过 NMR 光谱法和常规临床化学测量的 CSF 葡萄糖和乳酸之间显示出很强的相关性（葡萄糖，R=0.87，n=173；乳酸，R=0.74，n=173）。NMR 光谱法共检测到 99 种代谢物；51 种在 CSF 和血清中均有检测到，16 种仅在 CSF 中检测到，32 种仅在血清中检测到。一些代谢物的 CSF 浓度随年龄和/或血脑屏障功能下降而增加。在不同疾病组中，代谢物的检测率总体相似。然而，在两组比较中，CSF 和血清中的绝对代谢物水平可区分多发性硬化症和神经退行性疾病（曲线下面积（AUC）=0.96）、多发性硬化症和帕金森病（AUC=0.89），以及帕金森病和对照组患者（AUC=0.91），这通过随机森林统计模型得到证实。使用 CSF 和血清中绝对代谢物水平的正交偏最小二乘判别分析也允许区分帕金森病和神经退行性疾病。与神经退行性疾病相比，帕金森病患者 CSF 中的丙酸水平约低 4 倍。