title: Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples: ELISA, electrochemiluminescence immunoassay and Simoa.
abstract: 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.forename: Jens
authors.initials: J
authors.lastname: Kuhle
authors.forename: Christian
authors.initials: C
authors.lastname: Barro
authors.forename: Ulf
authors.initials: U
authors.lastname: Andreasson
authors.forename: Tobias
authors.initials: T
authors.lastname: Derfuss
authors.forename: Raija
authors.initials: R
authors.lastname: Lindberg
authors.forename: Åsa
authors.initials: Å
authors.lastname: Sandelius
authors.forename: Victor
authors.initials: V
authors.lastname: Liman
authors.forename: Niklas
authors.initials: N
authors.lastname: Norgren
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
mesh_terms: D015415:Biomarkers / Q000097:blood* / Q000134:cerebrospinal fluid; D055664:Electrochemical Techniques / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D008163:Luminescent Measurements / Q000379:methods*; D009103:Multiple Sclerosis / Q000097:blood* / Q000134:cerebrospinal fluid*; D016900:Neurofilament Proteins / Q000097:blood* / Q000134:cerebrospinal fluid
chemical_list: D015415:Biomarkers; D016900:Neurofilament Proteins