title: Technical performance of a novel, fully automated electrochemiluminescence immunoassay for the quantitation of β-amyloid (1-42) in human cerebrospinal fluid.
abstract: Available assays for quantitation of the Alzheimer's disease (AD) biomarker amyloid-beta 1-42 (Aβ [1-42]) in cerebrospinal fluid demonstrate significant variability and lack of standardization to reference measurement procedures (RMPs). We report analytical performance data for the novel Elecsys β-amyloid (1-42) assay (Roche Diagnostics).
  
  
  
  Lot-to-lot comparability was tested using method comparison. Performance parameters were measured according to Clinical & Laboratory Standards Institute (CLSI) guidelines. The assay was standardized to a Joint Committee for Traceability in Laboratory Medicine (JCTLM) approved RMP.
  
  
  
  Limit of quantitation was <11.28 pg/mL, and the assay was linear throughout the measuring range (200-1700 pg/mL). Excellent lot-to-lot comparability was observed (correlation coefficients [Pearson's r] >0.995; bias in medical decision area <2%). Repeatability coefficients of variation (CVs) were 1.0%-1.6%, intermediate CVs were 1.9%-4.0%, and intermodule CVs were 1.1%-3.9%. Estimated total reproducibility was 2.0%-5.1%. Correlation with the RMP was good (Pearson's r, 0.93).
  
  
  
  The Elecsys β-amyloid (1-42) assay has high analytical performance that may improve biomarker-based AD diagnosis.
authors.affiliation: Roche Diagnostics GmbH, Penzberg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Bittner
authors.affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology, London, UK.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Clinical Chemistry, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Teunissen
authors.affiliation: Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Ostlund
authors.affiliation: Covance Central Laboratory Services, Indianapolis, IN, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Militello
authors.affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Andreasson
authors.affiliation: Clinical Chemistry, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Hubeek
authors.affiliation: Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: David
authors.initials: D
authors.lastname: Gibson
authors.affiliation: Covance Central Laboratory Services, Indianapolis, IN, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Chu
authors.affiliation: Roche Diagnostics GmbH, Penzberg, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Eichenlaub
authors.affiliation: Roche Diagnostics GmbH, Penzberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Heiss
authors.affiliation: Roche Diagnostics GmbH, Penzberg, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Kobold
authors.affiliation: Roche Diagnostics GmbH, Penzberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Leinenbach
authors.affiliation: Roche Diagnostics GmbH, Penzberg, Germany.
authors.forename: Kairat
authors.initials: K
authors.lastname: Madin
authors.affiliation: Roche Diagnostics GmbH, Penzberg, Germany.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Manuilova
authors.affiliation: Roche Diagnostics GmbH, Penzberg, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Rabe
authors.affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden. Electronic address: Kaj.Blennow@neuro.gu.se.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides; D015415:Biomarkers / Q000032:analysis / Q000134:cerebrospinal fluid*; D006801:Humans; D007118:Immunoassay / Q000295:instrumentation / Q000379:methods / Q000592:standards*; D049449:Luminescence; D010446:Peptide Fragments; D012015:Reference Standards; D015203:Reproducibility of Results
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer's disease; Amyloid; Amyloid-beta 1–42; Assay; Biomarker; Cerebrospinal fluid; Dementia; Diagnosis; Electrochemiluminescence; Immunoassay; Method comparison; Precision; Repeatability; Reproducibility; Variability