Wu Yonghua, Yang Xu, Li Xiaogang, Wang Haining, Wang Tiancheng
Department of Laboratory Medicine, Peking University Third Hospital, No.49, North Garden Road, Haidian District, Beijing, 100191, China.
Department of Neurology, Peking University Third Hospital, Beijing, China.
Neurol Sci. 2020 Jul;41(7):1865-1872. doi: 10.1007/s10072-020-04292-x. Epub 2020 Feb 21.
Homocysteine (Hcy) has been shown to be relevant in the pathogenesis of amyotrophic lateral sclerosis (ALS). Although the CSF Hcy changes were explored in patients with ALS previously, the outcomes were inconsistent, and the permeability of the blood-brain barrier (BBB) may involve in the process. The aim of this study was to investigate the relationship between concentration of Hcy and BBB integrity indicated by CSF/serum albumin ratio (Q).
CSF and plasma/serum levels of Hcy, folate, and vitamin B12 and other biochemical biomarkers such as albumin, β-microglobulin, high sensitive-C reactive protein (hs-CRP), microalbumin, immunoglobulin G (IgG), IgM, IgA, and complement 3 and 4 were analyzed in all 31 ALS patients and 34 controls. Routine CSF analysis including cells/leukocytes count, total protein, glucose, and chlorides were also performed.
CSF Hcy levels (0.50 ± 0.46 vs 0.25 ± 0.27 μmol/L) and Q (8.09 ± 3.03 vs 6.39 ± 2.21) were significantly higher in the ALS group than that in controls (P < 0.05). The generalized linear mixed model analysis showed that the CSF Hcy was positively correlated with Q in ALS patients (P < 0.05).
BBB permeability is increased in ALS patients. CSF Hcy level is associated with BBB integrity. Q is a significantly independent predisposing factor for CSF Hcy.
同型半胱氨酸（Hcy）已被证明与肌萎缩侧索硬化症（ALS）的发病机制相关。尽管先前已对ALS患者的脑脊液Hcy变化进行了研究，但结果并不一致，且血脑屏障（BBB）的通透性可能参与了这一过程。本研究的目的是探讨Hcy浓度与以脑脊液/血清白蛋白比值（Q）表示的BBB完整性之间的关系。
对31例ALS患者和34例对照者的脑脊液和血浆/血清中的Hcy、叶酸、维生素B12以及其他生化生物标志物，如白蛋白、β-微球蛋白、高敏C反应蛋白（hs-CRP）、微量白蛋白、免疫球蛋白G（IgG）、IgM、IgA以及补体3和4进行了分析。还进行了脑脊液常规分析，包括细胞/白细胞计数、总蛋白、葡萄糖和氯化物。
ALS组的脑脊液Hcy水平（0.50±0.46 vs 0.25±0.27 μmol/L）和Q值（8.09±3.03 vs 6.39±2.21）显著高于对照组（P<0.05）。广义线性混合模型分析显示，ALS患者的脑脊液Hcy与Q呈正相关（P<0.05）。
ALS患者的血脑屏障通透性增加。脑脊液Hcy水平与血脑屏障完整性相关。Q是脑脊液Hcy的一个显著独立危险因素。
