@article{2999382,
    title = "The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers",
    author = "Mattsson, N. and Andreasson, U. and Persson, S. and Arai, H. and Batish, S.D. and Bernardini, S. and Bocchio-Chiavetto, L. and Blankenstein, M.A. and Carrillo, M.C. and Chalbot, S. and Coart, E. and Chiasserini, D. and Cutler, N. and Dahlfors, G. and Duller, S. and Fagan, A.M. and Forlenza, O. and Frisoni, G.B. and Galasko, D. and Galimberti, D. and Hampel, H. and Handberg, A. and Heneka, M.T. and Herskovits, A.Z. and Herukka, S.-K. and Holtzman, D.M. and Humpel, C. and Hyman, B.T. and Iqbal, K. and Jucker, M. and Kaeser, S.A. and Kaiser, E. and Kapaki, E. and Kidd, D. and Klivenyi, P. and Knudsen, C.S. and Kummer, M.P. and Lui, J. and Lladó, A. and Lewczuk, P. and Li, Q.-X. and Martins, R. and Masters, C. and McAuliffe, J. and Mercken, M. and Moghekar, A. and Molinuevo, J.L. and Montine, T.J. and Nowatzke, W. and O'Brien, R. and Otto, M. and Paraskevas, G.P. and Parnetti, L. and Petersen, R.C. and Prvulovic, D. and De Reus, H.P.M. and Rissman, R.A. and Scarpini, E. and Stefani, A. and Soininen, H. and Schröder, J. and Shaw, L.M. and Skinningsrud, A. and Skrogstad, B. and Spreer, A. and Talib, L. and Teunissen, C. and Trojanowski, J.Q. and Tumani, H. and Umek, R.M. and Van Broeck, B. and Vanderstichele, H. and Vecsei, L. and Verbeek, M.M. and Windisch, M. and Zhang, J. and Zetterberg, H. and Blennow, K.",
    journal = "American Journal of Alzheimer's Disease and other Dementias",
    year = "2011",
    volume = "7",
    number = "4",
    pages = "386-395.e6",
    publisher = "ELSEVIER SCIENCE INC 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA",
    issn = "1533-3175",
    doi = "10.1016/j.jalz.2011.05.2243",
    keywords = "amyloid beta protein;  phosphorylated tau;  tau protein;  unclassified drug, Alzheimer disease;  article;  cerebrospinal fluid;  disease marker;  health program;  laboratory diagnosis;  measurement;  priority journal;  quality control",
    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. © 2011 The Alzheimer's Association. All rights reserved."
}