title: Round robin test on quantification of amyloid-β 1-42 in cerebrospinal fluid by mass spectrometry.
abstract: BACKGROUND
  Cerebrospinal fluid (CSF) amyloid-β 1-42 (Aβ42) is an important biomarker for Alzheimer's disease, both in diagnostics and to monitor disease-modifying therapies. However, there is a great need for standardization of methods used for quantification. To overcome problems associated with immunoassays, liquid chromatography-tandem mass spectrometry (LC-MS/MS) has emerged as a critical orthogonal alternative.
  
  
  METHODS
  We compared results for CSF Aβ42 quantification in a round robin study performed in four laboratories using similar sample preparation methods and LC-MS instrumentation.
  
  
  RESULTS
  The LC-MS results showed excellent correlation between laboratories (r(2) >0.98), high analytical precision, and good correlation with enzyme-linked immunosorbent assay (r(2) >0.85). The use of a common reference sample further decreased interlaboratory variation.
  
  
  CONCLUSIONS
  Our results indicate that LC-MS is suitable for absolute quantification of Aβ42 in CSF and highlight the importance of developing a certified reference material.
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Salgrenska Academy, University of Gothenburg, Mölndal, Sweden. Electronic address: josef.pannee@neuro.gu.se.
authors.forename: Josef
authors.initials: J
authors.lastname: Pannee
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Salgrenska Academy, University of Gothenburg, Mölndal, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Gobom
authors.affiliation: Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Shaw
authors.affiliation: Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Korecka
authors.affiliation: Waters Corporation, Milford, MA, USA.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Chambers
authors.affiliation: Waters Corporation, Milford, MA, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Lame
authors.affiliation: Chromatographic Sciences Department, PPD Laboratories, Richmond, VA, USA.
authors.forename: Rand
authors.initials: R
authors.lastname: Jenkins
authors.affiliation: Chromatographic Sciences Department, PPD Laboratories, Richmond, VA, USA.
authors.forename: William
authors.initials: W
authors.lastname: Mylott
authors.affiliation: Medical & Scientific Relations Division, Alzheimer's Association, Chicago, IL, USA.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Carrillo
authors.affiliation: Institute for Reference Materials and Measurements (IRMM), Joint Research Centre, European Commission, Geel, Belgium.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Zegers
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Salgrenska Academy, University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology, London, UK.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Salgrenska Academy, University of Gothenburg, Mölndal, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Salgrenska Academy, University of Gothenburg, Mölndal, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Portelius
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay / Q000592:standards; D006801:Humans; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D012015:Reference Standards; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)
keywords: Amyloid beta; Cerebrospinal fluid; Interlaboratory study; Mass spectrometry