Abstract
ObjectivesThe aim of this study was to identify CSF and serum factors as biomarkers that may aid in distinguishing ALS patients from control subjects and predicting ALS progression as well as prognosis.MethodsSerum and CSF samples from 105 patients with ALS and 56 control subjects were analyzed for 13 factors using ELISA. The revised ALS functional rating scale (ALSFRS‐r) was used to evaluate the overall functional status of ALS patients, and we also followed up with ALS patients either by phone or with clinic visits for five years after enrollment in this study. Finally, we examined the correlations between factor levels and various clinical parameters and evaluated the predictive value for prognosis through a multivariate statistic model.ResultsA total of eight factors were obviously elevated in CSF, and twelve markers were increased in serum. In the correlation analyses, there were trends toward higher bFGF, VEGF, MIP‐1α levels in ALS with a longer disease duration and slower disease progression in both CSF and serum. Higher MCP‐1 levels were associated with worse disease severity and faster progression, and the IFN‐γ levels were positively associated with disease progression in either CSF or serum. Finally, a better prognosis was observed with higher levels bFGF in CSF and VEGF in CSF and serum; conversely, patients with higher levels of IFN‐γ in the CSF had shorter overall survival.ConclusionsWe demonstrated that a factor profile of ALS patients is distinct from control subjects and may be useful in clinical practice and therapeutic trials.
Highlights
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that affects motor neurons in the brain and spinal cord leading to paralysis and eventually death (Hardiman, Van den Berg, & Kiernan, 2011)
We previously reported that several cytokines are elevated in the CSF and serum of ALS patients (Gao, Zhou, Cai, Gong, & Zang, 2014; Gong, Gao, Guo, Lu, & Zang, 2015; Liu, Gao, & Zang, 2015; Yang, Gao, Wu, Zhang, & Zang, 2016)
We found that bFGF, VEGF, and MIP-1α levels in the CSF and serum were positively correlated with disease duration (Table 3 and Figure 1), whereas opposing results were obtained when their correlation with disease progression rate (DPR) was analyzed (Table 5 and Figure 3)
Summary
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that affects motor neurons in the brain and spinal cord leading to paralysis and eventually death (Hardiman, Van den Berg, & Kiernan, 2011). There have been various ALS biomarker studies published with more ongoing, with special attention focused on identifying biomarkers in CSF or serum. Most of these studies have examined changes of individual biomarkers that might distinguish patients with ALS from healthy control subjects (Lu et al, 2015; Takahashi et al, 2015), but it is likely more appropriate to identify panels of biomarkers rather than focusing on a single factor to increase their specificity to ALS. A panel of biomarkers has been detected in either
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