A multi-center study of neurofilament assay reliability and inter-laboratory variability

Elizabeth Gray, Patrick Oeckl, Maria D.M. Amador, Ulf Andreasson, Jiyan An, Kaj Blennow, Robert Bowser, Maxim De Schaepdryver, Amanda Heslegrave, Jens Kuhle, Aleksandra Maceski, Marleen Koel-Simmelink, Foudil Lamari, Vittoria Lombardi, Andrea Malaspina, Irina Nilsson, Koen Poesen, François Salachas, Petra Steinacker, Charlotte E. TeunissenPhilip Van Damme, Henrik Zetterberg, Albert Ludolph, Andreas Jeromin, Martin R. Turner*, Markus Otto

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Objectives: Significantly elevated levels of neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH) have been described in the blood and cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis (ALS) patients. The aim of this study was to evaluate the analytical performance of different neurofilament assays in a round robin with 10 centers across Europe/U.S. Methods: Serum, plasma and CSF samples from a group of five ALS and five neurological control patients were distributed across 10 international specialist neurochemical laboratories for analysis by a range of commercial and in-house neurofilament assays. The performance of all assays was evaluated for their ability to differentiate between the groups. The inter-assay coefficient of variation was calculated where appropriate from sample measurements performed across multiple laboratories using the same assay. Results: All assays could differentiate ALS patients from controls in CSF. Inter-assay coefficient of variation of analytical platforms performed across multiple laboratories varied between 6.5% and 41.9%. Conclusions: This study is encouraging for the growing momentum toward integration of neurofilament measurement into the specialized ALS clinic. It demonstrates the importance of ‘round robin’ studies necessary to ensure the analytical quality required for translation to the routine clinical setting. A standardized neurofilament probe is needed which can be used as international benchmark for analytical performance in ALS.

Original languageEnglish
Pages (from-to)452-458
Number of pages7
JournalAmyotrophic lateral sclerosis and frontotemporal degeneration
Volume21
Issue number5-6
DOIs
Publication statusPublished - 2 Jul 2020

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