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Alzheimer`s & Dementia

Year: 2011  |  Volume: 7  |  Issue: 4  |  Page No.: 386 - 395

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 Galimberti, Harald Hampel, Aase Handberg, Michael T. Heneka, Adrianna Z. Herskovits, Sanna-Kaisa Herukka, David M. Holtzman, Christian Humpel, Bradley T. Hyman, Khalid Iqbal, Khalid Iqbal, Stephan A. Kaeser, Elmar Kaiser, Elisabeth Kapaki, Daniel Kidd, Peter Klivenyi, Cindy S. Knudsen, Markus P. Kummer, James Lui, Albert Llado, Piotr Lewczuk, Qiao-Xin Li, Ralph Martins, Colin Masters, John McAuliffe, Marc Mercken, Abhay Moghekar, Jose 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 Schroder, Leslie M. Shaw, Anders Skinningsrud, Brith Skrogstad and Annette Spreer


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 Molndal 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.

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