Jens Kühle; Christian Barro; Ulf Andréasson; Tobias Derfuß; Raija L.P. Lindberg; Åsa Sandelius; Victor Liman; Niklas Norgren; Kaj Blennow; Henrik Zetterberg · 2016 · Clinical Chemistry and Laboratory Medicine (CCLM)
Paper
BACKGROUND: Neuronal damage is the morphological substrate of persisting neurological disability. Neurofilaments (Nf) are specific cytoskeletal proteins of neurons and their quantification has shown encouraging results as a biomarker for axonal injury. METHODS: We aimed at comparing a widely used conventional ELISA for Nf light chain (NfL) with an electrochemiluminescence-based method (ECL assay) and a newly developed single-molecule array (Simoa) method in clinically relevant cerebrospinal fluid (CSF) and serum samples. RESULTS: Analytical sensitivity was 0.62 pg/mL for Simoa, 15.6 pg/mL for the ECL assay, and 78.0 pg/mL for the ELISA. Correlations between paired CSF and serum samples were strongest for Simoa (r=0.88, p<0.001) and the ECL assay (r=0.78, p<0.001) and weaker for ELISA measurements (r=0.38, p=0.030). CSF NfL measurements between the platforms were highly correlated (r=1.0, p<0.001). Serum NfL levels were highly related between ECL assay and Simoa (r=0.86, p<0.001), and this was less visible between ELISA-ECL assay (r=0.41, p=0.018) and ELISA-Simoa (r=0.43, p=0.013). Multiple sclerosis (MS) patients had significantly higher serum NfL levels than controls when measured with Simoa (p=0.001) but not with the other platforms. CONCLUSIONS: We found Simoa to be more sensitive than ELISA or the ECL assay. Our results support the feasibility of quantifying NfL in serum; the results correlate with the more-established CSF NfL test. The highly sensitive Simoa technology deserves further studies in larger patient cohorts to clarify whether serum NfL could be used in the future to measure disease severity and determine prognosis or response to treatment interventions in neurological diseases.
Analysis
This study compares the sensitivity and correlation of ELISA, ECL, and Simoa platforms for quantifying neurofilament light chain (NfL) in CSF and serum, finding Simoa to be the most sensitive and demonstrating its potential for clinical use.
Discovery
Dietmar Rudolf Thal; Koen Poesen; Rik Vandenberghe; Steffi De Meyer
Nicholas J. Ashton; Wagner S. Brum; Guglielmo Di Molfetta; Andréa Lessa Benedet; Burak Arslan; Erin M. Jonaitis; Rebecca E. Langhough; Karly Alex Cody; Rachael E. Wilson; Cynthia M. Carlsson; Eugeen Vanmechelen; Laia Montoliu‐Gaya; Juan Lantero‐Rodriguez; Nesrine Rahmouni; Cécile Tissot; Jenna Stevenson; Stijn Servaes; Joseph Therriault; Tharick A. Pascoal; Alberto Lleó; Daniel Alcolea; Juan Fortea; Pedro Rosa‐Neto; Sterling C. Johnson; Andreas Jeromin; Kaj Blennow; Henrik Zetterberg
Charles Bernick; Guogen Shan; Aaron Ritter; Nicholas J. Ashton; Kaj Blennow; Juan Lantero‐Rodriguez; Anniina Snellman; Henrik Zetterberg
Fernando González‐Ortiz; Michael Turton; Przemysław R. Kac; Denis S. Smirnov; Enrico Premi; Roberta Ghidoni; Luisa Benussi; Valentina Cantoni; Claudia Saraceno; Jasmine Rivolta; Nicholas J. Ashton; Barbara Borroni; Douglas Galasko; Peter Harrison; Henrik Zetterberg; Kaj Blennow; Thomas K. Karikari
Oskar Hansson; Rebecca M. Edelmayer; Adam L. Boxer; María C. Carrillo; Michelle M. Mielke; Gil D. Rabinovici; Stephen Salloway; Reisa A. Sperling; Henrik Zetterberg; Charlotte E. Teunissen
Henrik Zetterberg; Kaj Blennow
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