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.
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.
Authors: Frederick K Korley; Jason Goldstick; Mitra Mastali; Jennifer E Van Eyk; William Barsan; William J Meurer; Jeremy Sussman; Hayley Falk; Deborah Levine Journal: Stroke Date: 2019-05-29 Impact factor: 7.914
Authors: Allison Given Chunyk; Alison Joyce; Saloumeh K Fischer; Mark Dysinger; Alvydas Mikulskis; Andreas Jeromin; Rosemary Lawrence-Henderson; Dana Baker; David Yeung Journal: AAPS J Date: 2017-12-01 Impact factor: 4.009
Authors: Anne-Katrin Pröbstel; Xiaoyuan Zhou; Ryan Baumann; Sven Wischnewski; Michael Kutza; Olga L Rojas; Katrin Sellrie; Antje Bischof; Kicheol Kim; Akshaya Ramesh; Ravi Dandekar; Ariele L Greenfield; Ryan D Schubert; Jordan E Bisanz; Stephanie Vistnes; Khashayar Khaleghi; James Landefeld; Gina Kirkish; Friederike Liesche-Starnecker; Valeria Ramaglia; Sneha Singh; Edwina B Tran; Patrick Barba; Kelsey Zorn; Johanna Oechtering; Karin Forsberg; Lawrence R Shiow; Roland G Henry; Jennifer Graves; Bruce A C Cree; Stephen L Hauser; Jens Kuhle; Jeffrey M Gelfand; Peter M Andersen; Jürgen Schlegel; Peter J Turnbaugh; Peter H Seeberger; Jennifer L Gommerman; Michael R Wilson; Lucas Schirmer; Sergio E Baranzini Journal: Sci Immunol Date: 2020-11-20