title: Validation of a Commercial Chemiluminescence Immunoassay for the Simultaneous Measurement of Three Different Amyloid-β Peptides in Human Cerebrospinal Fluid and Application to a Clinical Cohort.
abstract: A comprehensive assay validation campaign of a commercially available chemiluminescence multiplex immunoassay for the simultaneous measurement of the amyloid-β peptides Aβ38, Aβ40, and Aβ42 in human cerebrospinal fluid (CSF) is presented. The assay quality parameters we addressed included impact of sample dilution, parallelism, lower limits of detection, lower limits of quantification, intra- and inter-assay repeatability, analytical spike recoveries, and between laboratory reproducibility of the measurements. The assay performed well in our hands and fulfilled a number of predefined acceptance criteria. The CSF levels of Aβ40 and Aβ42 determined in a clinical cohort (n = 203) were statistically significantly correlated with available ELISA data of Aβ1-40 (n = 158) and Aβ1-42 (n = 179) from a different laboratory. However, Bland-Altman method comparison indicated systematic differences between the assays. The data presented here furthermore indicate that the CSF concentration of Aβ40 can surrogate total CSF Aβ and support the hypothesis that the Aβ42/Aβ40 ratio outperforms CSF Aβ42 alone as a biomarker for Alzheimer's disease due to a normalization to total Aβ levels.
authors: Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Georg-August-University, Goettingen, Germany.
authors: Hans-W
authors: HW
authors: Klafki
authors: LVR-Klinikum Essen, Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany.
authors: Henning
authors: H
authors: Hafermann
authors: MicroDiscovery GmbH, Berlin, Germany.
authors: Chris
authors: C
authors: Bauer
authors: LVR-Klinikum Essen, Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany.
authors: Ute
authors: U
authors: Haussmann
authors: Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Georg-August-University, Goettingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), Research Site Goettingen, Germany.
authors: Inga
authors: I
authors: Kraus
authors: MicroDiscovery GmbH, Berlin, Germany.
authors: Johannes
authors: J
authors: Schuchhardt
authors: Memory Clinic at the Elisabeth Hospital, Geriatrie-Zentrum Haus Berge, Essen, Germany.
authors: Stephan
authors: S
authors: Muck
authors: LVR-Klinikum Essen, Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany.
authors: Norbert
authors: N
authors: Scherbaum
authors: Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Georg-August-University, Goettingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), Research Site Goettingen, Germany.
authors: Jens
authors: J
authors: Wiltfang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000592:standards; D005260:Female; D006801:Humans; D049449:Luminescence; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)
keywords: Alzheimer’s disease; amyloid-β peptide; assay validation; biomarker; cerebrospinal fluid; multiplex immunoassay