VEGF Levels In CSF And Serum In Mild ALS Patients

BackgroundsAmyotrophic lateral sclerosis(ALS) is an incurable neurodegenerative disorder involving both upper and lower motor neurons in the cerebral cortex, brainstem and spinal cord. Most cases of ALS are sporadic in occurrence, but about 5%-10% of cases are familial. Recently, a deficit in the presence of endogenous neurotrophic factors may play a key role in the attenuation of the progression of ALS.Vascular endothelial growth factor(VEGF) has pro-survival effects on some neuronal cells, protects against experimentally induced cell death, stimulates axonal growth, stimulates neurogenesis, regulates neuronal migration, and promotes dendrite patterning and synaptic plasticity. VEGF was originally described as a factor with a regulatory role in vascular growth and development, and now it also functions as a neurotrophic factor protecting motoneurons from insults such as oxidative stress, hypoxia and glutamate-excitotoxicity. However the role of VEGF in ALS is still unclear, it may have a prognostic and evaluating potential for ALS.ObjectiveAs initial symptoms and physical signs of ALS patients are similar to many other diseases leading to the difficulties of ALS early diagnosis, and there is no specific diagnostic test, therefore identification of ALS-related biomarkers may play an important role in early diagnosis and help us understand the pathogenesis of the disease. The aim of this study is to measure cerebrospinalfluid(CSF) and serum VEGF levels in patients with mild ALS, and to investigate whether there are correlations between CSF and serum VEGF levels and clinical parameters of the disease, such as disease duration, disease progression rate(DPR) and ALS functional rating scale revised(ALSFRS-R) score, and whether VEGF has a prognostic and evaluating potential for ALS. MethodsFrom 2006 to 2013, in the Neurology Department of Tianjin First Center Hospital, serum samples from 30 patients with mild ALS and 20 healthy individuals and CSF samples from part patients, 14 mild ALS patients and 10 patients with tension-type-headache, were collected for VEGF levels by enzyme-linked immunosorbent assay(ELISA). All statistical analyses and graphs were performed using GraphPad Prism Ver 5. ResultsCompared to CSF control group(535.40±106.57pg/ml) and serum control group(560.10±50.33pg/ml), VEGF levels were found to increase significantly in CSF(669.28±116.74pg/ml) and serum(1384.93±623.63pg/ml) in patients with mild ALS(P=0.009 and P<0.001); they were positively and significantly(r=0.5463, P=0.0432 and r=0.4168, P=0.0219) correlated with the disease duration in ALS patients and inversely and significantly(r=-0.5360, P=0.0482 and r=-0.3857, P=0.0353) correlated with DPR of ALS patients. Moreover, CSF and serum from ALS patients with long duration(>12months) and slow DPR(<1) revealed higher VEGF levels as compared to ALS patients with short duration(≤12months) and rapid DPR(≥1). ConclusionsBy detecting VEGF levels in CSF and serum in mild ALS patients, our findings suggest1) Compared to control group, VEGF levels were found to increase significantly in CSF and serum in patients with mild ALS; they were positively correlated with the disease duration of ALS patients and inversely correlated with DPR of ALS patients. 2) CSF and serum from ALS patients with long duration and slow DPR revealed higher VEGF levels as compared to ALS patients with short duration and rapid DPR. 3) VEGF upregulation may indicate an activation of compensatory responses in ALS which may reflect or in fact account for increased duration and slow DPR. 4) We propose that VEGF may be a useful biomarker having the prognostic and evaluating potential for ALS.