NLRP3 inflammasome CSF expression and neuropsychological changes in idiopathic normal pressure hydrocephalus

Object. Inflammasomes are multiprotein complexes involved in the pathogenesis of neurodegenerative diseases. Aim of this study is to evaluate the expression of Nod-like receptor protein 3 (NLRP3) in cerebrospinal fluid (CSF) of idiopathic normal pressure hydrocephalus (iNPH). Patients and methods. Eleven patients with iNPH (iNPH group), 8 patients excluded for iNPH criteria (non iNPH group) and 11 controls were enrolled. CSF samples were collected before and after 48 hours of extended lumbar drainage (ELD). Western blot analysis was performed for NLRP3, caspase-1 and interleukin (IL)-1b. Results. Results demonstrated that NLRP3 was upregulated iNPH group and non iNPH group, compared to controls. Expression of NLRP3 was significantly increased in iNPH group. CSF removal led to the reduction of NLRP3 expression in both group of patients. This downregulation was more significant in iNPH group. Pearson analysis evidenced a negative correlation between NLRP3 expression and gait, balance and neuropsychological parameters in iNPH group. NLRP3 levels were significantly higher in CSF of patients with worse scores, as well as the post ELD NLRP3 reduction was associated with an improvement of outcome. A marked decrease of caspase-1 and IL-1b levels, NLRP3 downstream mediators was observed after ELD. Conclusions. Our study suggests that NLRP3 inflammasome is involved in iNPH pathogenesis and might be a predictive biomarker of shunt response in iNPH patients.