Multicenter validation of CSF neurofilaments as diagnostic biomarkers for ALS

• Published in: Amyotrophic lateral sclerosis and frontotemporal degeneration Vol. 17; no. 5-6; pp. 404 - 413
• Main Authors: Oeckl, Patrick, Jardel, Claude, Salachas, François, Lamari, Foudil, Andersen, Peter M., Bowser, Robert, de Carvalho, Mamede, Costa, Júlia, van Damme, Philip, Gray, Elizabeth, Grosskreutz, Julian, Hernández-Barral, María, Herukka, Sanna-Kaisa, Huss, André, Jeromin, Andreas, Kirby, Janine, Kuzma-Kozakiewicz, Magdalena, Amador, Maria del Mar, Mora, Jesús S., Morelli, Claudia, Muckova, Petra, Petri, Susanne, Poesen, Koen, Rhode, Heidrun, Rikardsson, Anna-Karin, Robberecht, Wim, Rodríguez Mahillo, Ana I., Shaw, Pamela, Silani, Vincenzo, Steinacker, Petra, Turner, Martin R., Tüzün, Erdem, Yetimler, Berrak, Ludolph, Albert C., Otto, Markus
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 17.08.2016
• Subjects: Adult; Aged; amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - cerebrospinal fluid; biomarker; Biomarkers - cerebrospinal fluid; Cerebrospinal fluid; Enzyme-Linked Immunosorbent Assay; Europe; Female; Humans; Intermediate Filaments - metabolism; Male; Middle Aged; neurofilament; Phosphorylation; Reproducibility of Results; round robin; Statistics, Nonparametric; United States; Cerebrospinal fluid; round robin; biomarker; neurofilament; amyotrophic lateral sclerosis
• ISSN: 2167-8421; 2167-9223; 2167-9223
• DOI: 10.3109/21678421.2016.1167913

OBJECTIVE: Neurofilaments are leading neurochemical biomarkers for amyotrophic lateral sclerosis (ALS). Here, we investigated the effect of preanalytical factors on neurofilament concentrations in cerebrospinal fluid (CSF) in a "reverse" round-robin with 15 centers across Europe/U.S. METHODS: Samples from ALS and control patients (5/5 each center, n = 150) were analyzed for phosphorylated neurofilament heavy chain (pNfH) and neurofilament light chain (NfL) at two laboratories. RESULTS: CSF pNfH was increased (p < 0.05) in ALS in 10 out of 15 centers and NfL in 5 out of 12 centers. The coefficient of variation (CV%) of pNfH measurements between laboratories was 18.7 ± 19.1%. We calculated a diagnostic cut-off of >568.5 pg/mL for pNfH (sensitivity 78.7%, specificity 93.3%) and >1,431pg/mL for NfL (sensitivity 79.0%, specificity 86.4%). CONCLUSION: Values in ALS patients are already comparable between most centers, supporting eventual implementation into clinical routine. However, continuous quality control programs will be necessary for inclusion in the diagnostic work-up.