Plasma Neurofilament Light (NfL) in Patients Affected by Niemann-Pick Type C Disease (NPCD).

Andrea Dardis,Stefania Zampieri,Maurizio Scarpa,Romina Milanic,Rosalia Maria Da Riol,Agata Fiumara,Annalisa Sechi,Jessica Biasizzo,Lucia Santoro,Martina Fabris,Eleonora Pavan,Maximiliano Ormazabal

doi:10.3390/jcm10204796

Abstract

(1) Background: Niemann–Pick type C disease (NPCD) is an autosomal recessive lysosomal 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 presenting 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 sampling, 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.

Highlights

Plasma NF light (NfL) levels were measured in 75 healthy controls and 26 patients affected by Niemann–Pick type C disease (NPCD) (24 NPC1 and 2 NPC2)
Serial samples obtained during regular follow-up visits were available for 8/26 NPCD patients
In this work we explored the role of plasma NfL as a possible biomarker in NPCD

Summary

Introduction

Niemann–Pick type C disease (NPCD-MIM 257220; MIM607625) is an autosomal recessive neurovisceral lysosomal storage disorder due to mutations in the NPC1 (95% of patients) or NPC2 genes, encoding two proteins involved in the intracellular trafficking of cholesterol and other lipids. The deficiency of either of them leads to the accumulation of endocytosed unesterified cholesterol and other lipids within the lysosome/late endosome compartment [1]. The clinical presentation of the disease is extremely variable and the age at onset ranges from the perinatal period to adulthood. The disease is typically characterized by visceral and neurological signs and symptoms that follow an independent clinical course

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Conclusion