Plasma neurofilament light (NfL) in patients affected by niemann–pick type C disease (NPCD)

Abstract

Background: Niemann–Pick type C disease (NPCD) is an autosomal recessive lysoso-mal storage disorder caused by mutations in the NPC1 or NPC2 genes. The clinical presentation is characterized by visceral and neurological involvement. Apart from a small group of patients pre-senting a severe perinatal form, all patients develop progressive and fatal neurological disease with an extremely variable age of onset. Different biomarkers have been identified; however, they poorly correlate with neurological disease. In this study we assessed the possible role of plasma NfL as a neurological disease-associated biomarker in NPCD. (2) Methods: Plasma NfL levels were measured in 75 healthy controls and 26 patients affected by NPCD (24 NPC1 and 2 NPC2; 39 samples). (3) Results: Plasma NfL levels in healthy controls correlated with age and were significantly lower in pediatric patients as compared to adult subjects (p = 0.0017). In both pediatric and adult NPCD patients, the plasma levels of NfL were significantly higher than in age-matched controls (p < 0.0001). Most importantly, plasma NfL levels in NPCD patients with neurological involvement were significantly higher than the levels found in patients free of neurological signs at the time of sam-pling, both in the pediatric and the adult group (p = 0.0076; p = 0.0032, respectively). Furthermore, in adults the NfL levels in non-neurological patients were comparable with those found in age-matched controls. No correlations between plasma NfL levels and NPCD patient age at sampling or plasma levels of cholestan 3β-5α-6β-triol were found. (4) Conclusions: These data suggest a promising role of plasma NfL as a possible neurological disease-associated biomarker in NPCD.