Blasco H, Veyrat-Durebex C, Bocca C, Patin F, Vourc'h P, Kouassi Nzoughet J, Lenaers G, Andres C R, Simard G, Corcia P, Reynier P
Université François-Rabelais, Inserm, U930, Tours, France.
Laboratoire de Biochimie, CHRU de Tours, France.
Sci Rep. 2017 Dec 15;7(1):17652. doi: 10.1038/s41598-017-17389-9.
Amyotrophic lateral sclerosis (ALS), the commonest adult-onset motor neuron disorder, is characterized by a survival span of only 2-5 years after onset. Relevant biomarkers or specific metabolic signatures would provide powerful tools for the management of ALS. The main objective of this study was to investigate the cerebrospinal fluid (CSF) lipidomic signature of ALS patients by mass spectrometry to evaluate the diagnostic and predictive values of the profile. We showed that ALS patients (n = 40) displayed a highly significant specific CSF lipidomic signature compared to controls (n = 45). Phosphatidylcholine PC(36:4), higher in ALS patients (p = 0.0003) was the most discriminant molecule, and ceramides and glucosylceramides were also highly relevant. Analysis of targeted lipids in the brain cortex of ALS model mice confirmed the role of some discriminant lipids such as PC. We also obtained good models for predicting the variation of the ALSFRS-r score from the lipidome baseline, with an accuracy of 71% in an independent set of patients. Significant predictions of clinical evolution were found to be correlated to sphingomyelins and triglycerides with long-chain fatty acids. Our study, which shows extensive lipid remodelling in the CSF of ALS patients, provides a new metabolic signature of the disease and its evolution with good predictive performance.
肌萎缩侧索硬化症（ALS）是最常见的成人发病的运动神经元疾病，其特征是发病后生存期仅为2至5年。相关生物标志物或特定代谢特征将为ALS的管理提供有力工具。本研究的主要目的是通过质谱法研究ALS患者的脑脊液（CSF）脂质组特征，以评估该特征的诊断和预测价值。我们发现，与对照组（n = 45）相比，ALS患者（n = 40）表现出高度显著的特定脑脊液脂质组特征。磷脂酰胆碱PC(36:4)在ALS患者中含量较高（p = 0.0003），是最具鉴别性的分子，神经酰胺和葡糖神经酰胺也高度相关。对ALS模型小鼠大脑皮质中靶向脂质的分析证实了一些鉴别性脂质如PC的作用。我们还从脂质组基线获得了预测ALSFRS-r评分变化的良好模型，在一组独立患者中的准确率为71%。发现临床进展的显著预测与鞘磷脂和含有长链脂肪酸的甘油三酯相关。我们的研究表明ALS患者脑脊液中存在广泛的脂质重塑，提供了该疾病及其进展的新代谢特征，具有良好的预测性能。
