Abstract
Amyotrophic lateral sclerosis (ALS) is an aggressive neurodegenerative disorder related to neuroinflammation that is associated with increased risk of thrombosis. We aimed to evaluate γ' fibrinogen plasma level (an in vivo variant of fibrinogen) as a biomarker in ALS, and to test its role as a predictor of disease progression and survival. Sixty-seven consecutive patients with ALS were followed and the results were compared with those from 82 healthy blood donors. Patients were clinically evaluated at the time of blood sampling and on follow-up (every 3 months for the beginning of the follow-up until death) by applying the revised ALS Functional Rating Scale. Human plasma γ' fibrinogen concentration was quantified using a specific two-site sandwich kit enzyme-linked immunosorbent assay. We found, for the first time, a positive association between γ' fibrinogen concentration and survival in ALS patients: patients with higher γ' fibrinogen plasma levels survived longer, and this finding was not influenced by confounders such as age, gender, respiratory impairment, or functionality (ALSFRS-R score). Since increased levels have a positive impact on outcome, this novel biomarker should be further investigated in ALS.
Highlights
Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disorder, in which there is degeneration of motor neurons in the spinal cord, brainstem, and motor cortex [1]
No statistically significant differences were observed between body mass index (BMI) of healthy donors’ (25.91 ± 3.85 kg/m2, mean ± standard deviation (SD)) and ALS patients’ (25.06 ± 2.74 kg/m2, mean ± SD; p = 0.27; Supplementary Table 1). γ’ fibrinogen levels were significantly higher in ALS patients [51.6 ± 24.5 mg/dL, mean ± SD, lower 95% confidence interval (CI) = 45.6; upper 95% confidence interval (CI) = 57.6) than in controls (38.7 ± 16.6 mg/dL; mean ± SD, lower 95% confidence interval (CI) = 35.0; upper 95% confidence interval (CI) = 42.3); p = 0.0006; Figure 1]
The plasma concentration of this fibrinogen variant was higher in ALS patients than in controls, which did not seem to depend on gender nor age
Summary
Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disorder, in which there is degeneration of motor neurons in the spinal cord, brainstem, and motor cortex [1]. Diagnosis can be difficult and slow, and there is no disease-modifying therapy available [1]. There is a pressing need for novel biomarkers to be used in clinical trials [2]. Respiratory dysfunction is the major determinant of functional impairment and death in ALS [3]. Hypoxia derives from respiratory muscles weakness, but its role in precipitating further neuronal damage or skeletal muscle dysfunction is unclear [4]. Episodes of vascular thrombosis are commonly reported in ALS, in general associated to immobility, but other risk factors have not been deeply explored [5]
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