The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers

Niklas Mattsson, Ulf Andreasson, Staffan Persson, Hiroyuki Arai, Sat Dev Batish, Sergio Bernardini, Luisella Bocchio-Chiavetto, Marinus A. Blankenstein, Maria C. Carrillo, Sonia Chalbot, Els Coart, Davide Chiasserini, Neal Cutler, Gunilla Dahlfors, Stefan Duller, Anne M. Fagan, Orestes Forlenza, Giovanni B. Frisoni, Douglas Galasko, Daniela GalimbertiHarald Hampel, Aase Handberg, Michael T. Heneka, Adrianna Z. Herskovits, Sanna Kaisa Herukka, David M. Holtzman, Christian Humpel, Bradley T. Hyman, Khalid Iqbal, Mathias Jucker, Stephan A. Kaeser, Elmar Kaiser, Elisabeth Kapaki, Daniel Kidd, Peter Klivenyi, Cindy S. Knudsen, Markus P. Kummer, James Lui, Albert Lladó, Piotr Lewczuk, Qiao Xin Li, Ralph Martins, Colin Masters, John McAuliffe, Marc Mercken, Abhay Moghekar, José Luis Molinuevo, Thomas J. Montine, William Nowatzke, Richard O'Brien, Markus Otto, George P. Paraskevas, Lucilla Parnetti, Ronald C. Petersen, David Prvulovic, Herman P.M. De Reus, Robert A. Rissman, Elio Scarpini, Alessandro Stefani, Hilkka Soininen, Johannes Schröder, Leslie M. Shaw, Anders Skinningsrud, Brith Skrogstad, Annette Spreer, Leda Talib, Charlotte Teunissen, John Q. Trojanowski, Hayrettin Tumani, Robert M. Umek, Bianca Van Broeck, Hugo Vanderstichele, Laszlo Vecsei, Marcel M. Verbeek, Manfred Windisch, Jing Zhang, Henrik Zetterberg, Kaj Blennow

Research output: Contribution to journalArticlepeer-review

268 Scopus citations

Abstract

Background: The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program. Methods: The program is open for laboratories using commercially available kits for Aβ, T-tau, or P-tau. CSF samples (aliquots of pooled CSF) are sent for analysis several times a year from the Clinical Neurochemistry Laboratory at the Mölndal campus of the University of Gothenburg, Sweden. Each round consists of three quality control samples. Results: Forty laboratories participated. Twenty-six used INNOTEST enzyme-linked immunosorbent assay kits, 14 used Luminex xMAP with the INNO-BIA AlzBio3 kit (both measure Aβ-(1-42), P-tau(181P), and T-tau), and 5 used Meso Scale Discovery with the Aβ triplex (AβN-42, AβN-40, and AβN-38) or T-tau kits. The total coefficients of variation between the laboratories were 13% to 36%. Five laboratories analyzed the samples six times on different occasions. Within-laboratory precisions differed considerably between biomarkers within individual laboratories. Conclusions: Measurements of CSF AD biomarkers show large between-laboratory variability, likely caused by factors related to analytical procedures and the analytical kits. Standardization of laboratory procedures and efforts by kit vendors to increase kit performance might lower variability, and will likely increase the usefulness of CSF AD biomarkers.

Original languageEnglish
Pages (from-to)386-395.e6
JournalAlzheimer's and Dementia
Volume7
Issue number4
DOIs
StatePublished - Jul 2011

Keywords

  • Alzheimer's disease
  • Biomarkers
  • Cerebrospinal fluid
  • External assurance
  • External control
  • Proficiency testing

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