Highlights
- •pNF-H of ALS in Asian
- •Paired plasma and CSF pNF-H
- •pNF-H has a correlation with TTG.
Abstract
Background and objective
Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by degeneration
of both upper and lower motor neurons. In this study, we aimed to measure both plasma
and cerebrospinal fluid (CSF) phosphorylated neurofilament heavy chain (pNF-H) levels
in patients with ALS, and determine if there is a correlation. We also evaluated plasma
and CSF pNF-H levels to investigate if this biomarker could predict the time to generalization
(TTG) in ALS better.
Methods
Paired plasma and CSF pNF-H levels of patients with ALS (n = 51), multiple system atrophy (n = 12) and controls (n = 30) were measured by monoclonal sandwich ELISA. TTG, which also indicates the time
of symptoms spreading from spinal or bulbar localization to both, was evaluated in
all ALS patients.
Results
We found a strong correlation between plasma and CSF pNF-H levels within individual
patients (r = 0.712, p < 0.001). The mean TTG in ALS patients was 22.9 months (range 1–84 months), and there was an inverse correlation between plasma (r = −0.661; p < 0.001)/CSF (r = −0.869; p < 0.001) pNF-H levels and TTG.
Conclusion
The correlation of plasma and CSF pNF-H levels would bring insight into the pathogenesis
of ALS. TTG might play an important role in the future study of ALS, as an early indicator
of survival.
Keywords
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References
- Prognostic factors in ALS: a critical review.Amyotroph. Lateral Scler. 2009; 10 (official publication of the World Federation of Neurology Research Group on Motor Neuron Diseases): 310-323
- Accumulation of phosphorylated neurofilaments in anterior horn motoneurons of amyotrophic lateral sclerosis patients.J. Neuropathol. Exp. Neurol. 1988; 47: 9-18
- SOD1 mutation is associated with accumulation of neurofilaments in amyotrophic lateral sclerosis.Ann. Neurol. 1996; 39: 128-131
- Defective axonal transport in a transgenic mouse model of amyotrophic lateral sclerosis.Nature. 1995; 375: 61-64
- Review of the multiple aspects of neurofilament functions, and their possible contribution to neurodegeneration.Mol. Neurobiol. 2008; 38: 27-65
- Neurofilament heavy chain side arm phosphorylation regulates axonal transport of neurofilaments.J. Cell Biol. 2003; 161: 489-495
- Neurofilament phosphoforms: surrogate markers for axonal injury, degeneration and loss.J. Neurol. Sci. 2005; 233: 183-198
- Cerebrospinal fluid neurofilament light chain levels: marker of progression to generalized amyotrophic lateral sclerosis.Eur. J. Neurol. 2015; 22 (the official journal of the European Federation of Neurological Societies): 215-218
- Time to generalisation as a predictor of prognosis in amyotrophic lateral sclerosis.J. Neurol. Neurosurg. Psychiatry. 2015;
- El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis.Amyotroph. Lateral Scler. Other Motor Neuron Disord. 2000; 1 (official publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases): 293-299
- The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS study group (phase III).J. Neurol. Sci. 1999; 169: 13-21
- Progression rate of ALSFRS-R at time of diagnosis predicts survival time in ALS.Neurology. 2006; 66: 265-267
- Multiple system atrophy: an update.Lancet Neurol. 2009; 8: 1172-1178
- Development and validation of the Unified Multiple System Atrophy Rating Scale (UMSARS).Mov. Disord. 2004; 19 (official journal of the Movement Disorder Society): 1391-1402
- A specific ELISA for measuring neurofilament heavy chain phosphoforms.J. Immunol. Methods. 2003; 278: 179-190
- A method to solubilise protein aggregates for immunoassay quantification which overcomes the neurofilament “hook” effect.J. Neurosci. Methods. 2011; 195: 143-150
- Axonal damage markers in cerebrospinal fluid are increased in ALS.Neurology. 2006; 66: 852-856
- Phosphorylated neurofilament heavy subunit (pNF-H) in peripheral blood and CSF as a potential prognostic biomarker in amyotrophic lateral sclerosis.J. Neurol. Neurosurg. Psychiatry. 2013; 84: 467-472
- Multicentre quality control evaluation of different biomarker candidates for amyotrophic lateral sclerosis.Amyotroph. Lateral Scler. Frontotemporal Degener. 2014; 15: 344-350
- Neurofilaments in the diagnosis of motoneuron diseases: a prospective study on 455 patients.J. Neurol. Neurosurg. Psychiatry. 2015;
- Multiple system atrophy.Lancet Neurol. 2004; 3: 93-103
- Combination of neurofilament heavy chain and complement C3 as CSF biomarkers for ALS.J. Neurochem. 2011; 117: 528-537
- Ultrastructure of blood-brain barrier and blood-spinal cord barrier in SOD1 mice modeling ALS.Brain Res. 2007; 1157: 126-137
- Evidence of compromised blood-spinal cord barrier in early and late symptomatic SOD1 mice modeling ALS.PLoS ONE. 2007; 2e1205
- ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration.Nat. Neurosci. 2008; 11: 420-422
- Impaired blood-brain and blood-spinal cord barriers in mutant SOD1-linked ALS rat.Brain Res. 2009; 1301: 152-162
- Aquaporin-4 overexpression in rat ALS model.Anat. Rec. 2009; 292: 207-213
- Disruption of neurovascular unit prior to motor neuron degeneration in amyotrophic lateral sclerosis.J. Neurosci. Res. 2011; 89: 718-728
- Hyperphosphorylated neurofilament NF-H is a serum biomarker of axonal injury.Biochem. Biophys. Res. Commun. 2005; 336: 1268-1277
- Survival of 793 patients with amyotrophic lateral sclerosis diagnosed over a 28-year period.Amyotroph. Lateral Scler. Other Motor Neuron Disord. 2004; 5 (official publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases): 208-212
- Prognosis in amyotrophic lateral sclerosis: a population-based study.Neurology. 2003; 60: 813-819
- Patients with amyotrophic lateral sclerosis and other neurodegenerative diseases have increased levels of neurofilament protein in CSF.J. Neurochem. 1996; 67: 2013-2018
- Neurofilaments levels as biomarkers in asymptomatic and symptomatic familial ALS.Ann. Neurol. 2015;
Article info
Publication history
Published online: June 01, 2016
Accepted:
May 31,
2016
Received in revised form:
May 10,
2016
Received:
January 31,
2016
Identification
Copyright
© 2016 Elsevier B.V. All rights reserved.
