A worldwide multicentre comparison of assays for cerebrospinal fluid biomarkers in Alzheimer's disease

N. A. Verwey, W. M. Van Der Flier, K. Blennow, C. Clark, S. Sokolow, P. P. De Deyn, D. Galasko, H. Hampel, T. Hartmann, E. Kapaki, L. Lannfelt, P. D. Mehta, L. Parnetti, A. Petzold, T. Pirttila, L. Saleh, A. Skinningsrud, J. C. V Swieten, M. M. Verbeek, J. WiltfangS. Younkin, P. Scheltens, M. A. Blankenstein

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Abstract

Background: Different cerebrospinal fluid (CSF) amyloid-beta 1-42 (Aβ 1-42), total Tau (Tau) and Tau phosphorylated at threonine 181 (P-Tau) levels are reported, but currently there is a lack of quality control programmes. The aim of this study was to compare the measurements of these CSF biomarkers, between and within centres. Methods: Three CSF-pool sampleswere distributed to 13 laboratories in 2004 and thesame sampleswere again distributed to 18 laboratories in 2008. In 2004 six laboratories measured Aβ 1-42, Tau and P-Tau and seven laboratories measured one or two of these marker(s) by enzyme-linked immunosorbent assays (ELISAs). In 2008, 12 laboratories measured all three markers, three laboratories measured one or two marker(s) by ELISAs and three laboratories measured the markers by Luminex. Results: In 2004, the ELISA intercentre coefficients of variance (interCV) were 31%, 21% and 13% for Aβ 1-42, Tau and P-Tau, respectively. These were 37%, 16% and 15%, respectively, in 2008. When we restricted the analysis to the Innotestw (N = 13) for Aβ 1-42, lower interCV were calculated (22%). The centres that participated in both years (N = 9) showed interCVs of 21%, 15% and 9% and intra-centre coefficients (intraCV) of variance of 25%,18% and 7% in 2008. Conclusions: The highest variability was found for Aβ 1-42. The variabilities for Tau and P-Tau were lower in both years. The centres that participated in both years showed a high intraCV comparable to their interCV, indicating that there is not only a high variation between but also within centres. Besides a uniform standardization of (pre)analytical procedures, the same assay should be used to decrease the inter/intracentre variation.

Original languageEnglish (US)
Pages (from-to)235-240
Number of pages6
JournalAnnals of Clinical Biochemistry
Volume46
Issue number3
DOIs
StatePublished - May 1 2009

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ASJC Scopus subject areas

  • Clinical Biochemistry

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Verwey, N. A., Van Der Flier, W. M., Blennow, K., Clark, C., Sokolow, S., De Deyn, P. P., Galasko, D., Hampel, H., Hartmann, T., Kapaki, E., Lannfelt, L., Mehta, P. D., Parnetti, L., Petzold, A., Pirttila, T., Saleh, L., Skinningsrud, A., V Swieten, J. C., Verbeek, M. M., ... Blankenstein, M. A. (2009). A worldwide multicentre comparison of assays for cerebrospinal fluid biomarkers in Alzheimer's disease. Annals of Clinical Biochemistry, 46(3), 235-240. https://doi.org/10.1258/acb.2009.008232