Increased cerebrospinal fluid adenosine 5'-triphosphate in patients with amyotrophic lateral sclerosis

BMC Neurology

Hideki Niimi¹  Atsushi Matsui¹  Isao Kitajima¹  Tomohiro Hayashi²  Nobuhiro Dougu²  Mamoru Yamamoto²  Hirofumi Konishi²  Takamasa Nukui²  Yuji Nakatsuji²  Ryoko Anada²  Noriyuki Matsuda²  Tomoyuki Sugimoto³ 

[1] Department of Clinical Laboratory and Molecular Pathology, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, 2630 Sugitani, 930-0194, Toyama, Japan;Department of Neurology, Faculty of Medicine, University of Toyama, 2630 Sugitani, 930-0194, Toyama, Japan;Faculty of Data Science, Graduate School of Data Science, University of Shiga, 1-1-1 Banba Hikone, 522-8522, Shiga, Japan;

关键词: ALS;    Cerebrospinal fluid;    ATP;    Biomarker;   

DOI  :  10.1186/s12883-021-02288-4

来源: Springer

【 摘 要 】

BackgroundExtracellular adenosine 5'-triphosphate (ATP) has been suggested to cause neuroinflammation and motor neuron degeneration by activating microglia and astrocytes in amyotrophic lateral sclerosis (ALS). Since we have developed a highly sensitive ATP assay system, we examined cerebrospinal fluid (CSF) ATP levels in patients with ALS whether it can be a useful biomarker in ALS.MethodsForty-eight CSF samples from 44 patients with ALS were assayed for ATP with a newly established, highly sensitive assay system using luciferase luminous reaction. CSF samples from patients with idiopathic normal pressure hydrocephalus (iNPH) were assayed as a control. Patients were divided into two groups depending on their disease severity, as evaluated using the Medical Research Council (MRC) sum score. Correlations between the CSF ATP levels and other factors, including clinical data and serum creatinine levels, were evaluated.ResultsCSF ATP levels were significantly higher in patients with ALS than in the iNPH (716 ± 411 vs. 3635 ± 5465 pmol/L, p < 0.01). CSF ATP levels were significantly higher in the more severe group than in the iNPH group (6860 ± 8312 vs. 716 ± 411 pmol/L, p < 0.05) and mild group (6860 ± 8312 vs. 2676 ± 3959 pmol/L, p < 0.05) respectively. ALS functional rating scale-revised (ALSFRS-R) (37.9 ± 5.7 vs. 42.4 ± 2.8, p < 0.01) and serum creatinine levels (0.51 ± 0.13 vs. 0.68 ± 0.23 mg/dL, p < 0.05) were significantly lower in the severe group than in the mild group respectively. A negative correlation of CSF ATP levels with MRC sum score was demonstrated in the correlation analysis adjusted for age and sex (r = -0.3, p = 0.08).ConclusionsExtracellular ATP is particularly increased in the CSF of patients with advanced ALS. CSF ATP levels may be a useful biomarker for evaluating disease severity in patients with ALS.

【 授权许可】

CC BY