title: Pre-analytical and analytical factors influencing Alzheimer's disease cerebrospinal fluid biomarker variability.
abstract: A panel of cerebrospinal fluid (CSF) biomarkers including total Tau (t-Tau), phosphorylated Tau protein at residue 181 (p-Tau) and β-amyloid peptides (Aβ42 and Aβ40), is frequently used as an aid in Alzheimer's disease (AD) diagnosis for young patients with cognitive impairment, for predicting prodromal AD in mild cognitive impairment (MCI) subjects, for AD discrimination in atypical clinical phenotypes and for inclusion/exclusion and stratification of patients in clinical trials. Due to variability in absolute levels between laboratories, there is no consensus on medical cut-off value for the CSF AD signature. Thus, for full implementation of this core AD biomarker panel in clinical routine, this issue has to be solved. Variability can be explained both by pre-analytical and analytical factors. For example, the plastic tubes used for CSF collection and storage, the lack of reference material and the variability of the analytical protocols were identified as important sources of variability. The aim of this review is to highlight these pre-analytical and analytical factors and describe efforts done to counteract them in order to establish cut-off values for core CSF AD biomarkers. This review will give the current state of recommendations.
authors.affiliation: Neurobiology Laboratory, Biochemistry and Molecular Biology Department, Hôpitaux de Lyon, Lyon, France; University of Lyon 1, CNRS UMR5292, INSERM U1028, BioRan, Lyon, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Fourier
authors.affiliation: Clinical, Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Portelius
authors.affiliation: Clinical, Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Clinical, Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Neurobiology Laboratory, Biochemistry and Molecular Biology Department, Hôpitaux de Lyon, Lyon, France; University of Lyon 1, CNRS UMR5292, INSERM U1028, BioRan, Lyon, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Quadrio
authors.affiliation: Neurobiology Laboratory, Biochemistry and Molecular Biology Department, Hôpitaux de Lyon, Lyon, France; University of Lyon 1, CNRS UMR5292, INSERM U1028, BioRan, Lyon, France; Société Française de Biologie Clinique (SFBC), Alzheimer Biomarkers group co-coordination, France. Electronic address: armand.perret-liaudet@chu-lyon.fr.
authors.forename: Armand
authors.initials: A
authors.lastname: Perret-Liaudet
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D019411:Clinical Laboratory Techniques / Q000295:instrumentation / Q000592:standards*; D003943:Diagnostic Techniques, Neurological / Q000295:instrumentation / Q000592:standards*; D006801:Humans; D015203:Reproducibility of Results
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers
keywords: Alzheimer diagnosis; Analytical confounders; Biomarkers; CSF; Dementia; Pre-analytical confounders