Urinary neopterin, a new marker of the neuroinflammatory status in amyotrophic lateral sclerosis

Objective To comprehensively assess whether neopterin in urine could be a candidate biomarker for determining the neuroinflammatory status in ALS. Methods We performed an observational, cross-sectional study in 81 pALS, 68 age- and sex-comparable healthy controls (HC), 14 patients affected by MS and 24 OND patients. ALS patients underwent a neurological evaluation to assess the global functional status evaluated by Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) and the disease progression rate. Urinary neopterin concentrations were determined by high-performance liquid chromatography method and were recorded at the time of first examination to assess their effect on disease severity and survival. Results Urinary neopterin was significantly higher in pALS (263.90 [198.71-474.90]) compared to MS (155.28 [131.74-190.38],p = < .001), OND patients (205.60 [158.96-299.41],p = 0.04) and HC (169.55 [134.91-226.10],p < .001). Moreover, a significant negative correlation was found between neopterin level and the severity of symptoms evaluated by ALSFRS-R total score (r = - 0.46,p < .001) and its subscores (bulbarr = - 0.34,p = 0.002; motorr = - 0.33,p = 0.003; respiratoryr = - 0.53,p < .001), also adjusting for the effect of sex, site of onset, age at evaluation and time from onset to evaluation. Conclusions Our finding indicates that urine neopterin is elevated in ALS, emphasizing the role of the cell-mediated inflammation in the disease. Moreover, whether confirmed in further studies, our results will underline the neopterin's potential use as non-invasive clinical biomarker of ALS, to discriminate patients possibly candidates to clinical interventions aimed to interfere the neuroinflammatory processes.