title: CSF Aβ1-42- an excellent but complicated Alzheimer's biomarker - a route to standardisation.
abstract: The 42 amino acid form of amyloid β (Aβ1-42) in cerebrospinal fluid (CSF) has been widely accepted as a central biomarker for Alzheimer's disease. Several immunoassays for CSF Aβ1-42are commercially available, but can suffer from between laboratory and batch-to-batch variability as well as lack of standardisation across assays. As a consequence, no general cut-off values have been established for a specific context of use (e.g., clinical diagnostics) and selection of individuals for enrolment in clinical trials (patient stratification) remains challenging. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) has initiated a working group for CSF proteins (WG-CSF) to facilitate standardisation of CSF Aβ1-42measurement results. The efforts of the IFCC WG-CSF include the development of certified reference materials (CRMs) and reference measurement procedures (RMPs) for key biomarkers. Two candidate RMPs for quantification of Aβ1-42in CSF based on liquid chromatography tandem mass spectrometry have been developed and tested in two ring trials. Furthermore, two commutability studies including native CSF pools, artificial CSF and spiked materials have been completed. On the basis of these studies, human CSF pools containing only endogenous Aβ1-42at three concentrations were selected as the format for future CRMs that are now being processed.
authors.affiliation: European Commission, Joint Research Centre, Institute for Reference Materials and Measurements, Geel, Belgium.
authors.forename: Julia
authors.initials: J
authors.lastname: Kuhlmann
authors.affiliation: Inst. of Neuroscience and Physiology Dept. of Psychiatry and Neurochemistry The Sahlgrenska Academy at University of Gothenburg Mölndal, Sweden; Clinical Neurochemistry LaboratorySahlgrenska University Hospital, MölndalSE-431 80 Mölndal Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Andreasson
authors.affiliation: Inst. of Neuroscience and Physiology Dept. of Psychiatry and Neurochemistry The Sahlgrenska Academy at University of Gothenburg Mölndal, Sweden; Clinical Neurochemistry LaboratorySahlgrenska University Hospital, MölndalSE-431 80 Mölndal Sweden.
authors.forename: Josef
authors.initials: J
authors.lastname: Pannee
authors.affiliation: Inst. of Neuroscience and Physiology Dept. of Psychiatry and Neurochemistry The Sahlgrenska Academy at University of Gothenburg Mölndal, Sweden; Clinical Neurochemistry LaboratorySahlgrenska University Hospital, MölndalSE-431 80 Mölndal Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Bjerke
authors.affiliation: Inst. of Neuroscience and Physiology Dept. of Psychiatry and Neurochemistry The Sahlgrenska Academy at University of Gothenburg Mölndal, Sweden; Clinical Neurochemistry LaboratorySahlgrenska University Hospital, MölndalSE-431 80 Mölndal Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Portelius
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: Tobias
authors.initials: T
authors.lastname: Bittner
authors.affiliation: Perelman School of Medicine, University of Pennsylvania, Department of Pathology and Laboratory Medicine, Philadelphia, PA, USA.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Korecka
authors.affiliation: Department of Chromatographic Sciences, PPD Laboratories, Richmond, VA, USA.
authors.forename: Rand G
authors.initials: RG
authors.lastname: Jenkins
authors.affiliation: ADx NeuroSciences NV, Gent, Belgium.
authors.forename: Hugo
authors.initials: H
authors.lastname: Vanderstichele
authors.affiliation: ADx NeuroSciences NV, Gent, Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: Stoops
authors.affiliation: Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany; Department of Neurodegeneration Diagnostics, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Lewczuk
authors.affiliation: Perelman School of Medicine, University of Pennsylvania, Department of Pathology and Laboratory Medicine, Philadelphia, PA, USA.
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Shaw
authors.affiliation: European Commission, Joint Research Centre, Institute for Reference Materials and Measurements, Geel, Belgium.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Zegers
authors.affiliation: European Commission, Joint Research Centre, Institute for Reference Materials and Measurements, Geel, Belgium.
authors.forename: Heinz
authors.initials: H
authors.lastname: Schimmel
authors.affiliation: Inst. of Neuroscience and Physiology Dept. of Psychiatry and Neurochemistry The Sahlgrenska Academy at University of Gothenburg Mölndal, Sweden; Clinical Neurochemistry LaboratorySahlgrenska University Hospital, MölndalSE-431 80 Mölndal Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Inst. of Neuroscience and Physiology Dept. of Psychiatry and Neurochemistry The Sahlgrenska Academy at University of Gothenburg Mölndal, Sweden; Clinical Neurochemistry LaboratorySahlgrenska University Hospital, MölndalSE-431 80 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 / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D019963:Clinical Chemistry Tests / Q000592:standards*; D006801:Humans; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D012015:Reference Standards
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer's disease; Aβ(1–42); Cerebrospinal fluid; Certified reference material; Reference measurement procedure