Abstract
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.
Highlights
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by degeneration of motor neurons in the motor cortex, brain stem, andNukui et al BMC Neurol (2021) 21:255 neuron death have been used as biomarkers for amyotrophic lateral sclerosis (ALS)
Patients with ALS were divided into two groups depending on the median value of the ALSFRS-R, and cerebrospinal fluid (CSF) adenosine 5’-triphosphate (ATP) levels were compared between these groups
CSF ATP levels were significantly higher in both ALS groups than those in the idiopathic normal pressure hydrocephalus (iNPH) group (716 ± 411 vs. 3379 ± 4300 pmol/L, 716 ± 411 vs. 3817 ± 6236, p < 0.05), but there were no significant differences in CSF ATP levels between the ALS groups (Fig. 3)
Summary
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by degeneration of motor neurons in the motor cortex, brain stem, andNukui et al BMC Neurol (2021) 21:255 neuron death have been used as biomarkers for ALS. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by degeneration of motor neurons in the motor cortex, brain stem, and. Neurofilament light chain (NfL) was reported to be increased in CSF in patients with ALS compared with other neurological diseases, and is suggested to be a diagnostic biomarker and a predictor of disease progression [7]. We assayed ATP levels in the CSF of patients with ALS to investigate whether it is a useful biomarker for disease severity or other clinical factors in ALS. Extracellular 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
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