Elevated cerebrospinal fluid homocysteine is associated with blood-brain barrier disruption in amyotrophic lateral scler
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ORIGINAL ARTICLE
Elevated cerebrospinal fluid homocysteine is associated with blood-brain barrier disruption in amyotrophic lateral sclerosis patients Yonghua Wu 1 & Xu Yang 1 & Xiaogang Li 2 & Haining Wang 3 & Tiancheng Wang 1 Received: 12 September 2019 / Accepted: 11 February 2020 # Fondazione Società Italiana di Neurologia 2020
Abstract Objectives 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 (Qalb). Methods CSF and plasma/serum levels of Hcy, folate, and vitamin B12 and other biochemical biomarkers such as albumin, β2microglobulin, 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. Results CSF Hcy levels (0.50 ± 0.46 vs 0.25 ± 0.27 μmol/L) and Qalb (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 Qalb in ALS patients (P < 0.05). Conclusions BBB permeability is increased in ALS patients. CSF Hcy level is associated with BBB integrity. Qalb is a significantly independent predisposing factor for CSF Hcy. Keywords Homocysteine . Folate . Vitamin B12 . Blood-brain barrier . Amyotrophic lateral sclerosis . Q-albumin
Introduction Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by neuronal loss and degeneration of motor neurons in the spinal cord, motor cortex, and brain stem that leads to paralysis and even death within several years after disease onset. However, the causes and pathophysiology of sporadic ALS have not been fully elucidated [1, 2].
* Tiancheng Wang [email protected] 1
Department of Laboratory Medicine, Peking University Third Hospital, No.49, North Garden Road, Haidian District, Beijing 100191, China
2
Department of Neurology, Peking University Third Hospital, Beijing, China
3
Department of Endocrinology and Metabolism, Peking University Third Hospital, Beijing, China
Homocysteine (Hcy), which is a pro-inflammatory thiolcontaining redox-active endogenous amino acid, is considered to be a risk factor for vascular diseases [3, 4]. Studies demonstrated that Hcy has neurotoxicity effects via the promotion of oxidative stress [5, 6]. Increased Hcy in cerebrospinal fluid (CSF) or plasma/serum has been found in neurodegenerative disorders, such as Parkinson’s disease (PD) [7, 8] and Alzheimer’s disease (AD) [9, 10]. In a study of transgenic mice, Hcy has been reported to be involved i
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