A worldwide multicentre comparison of assays for cerebrospinal fluid biomarkers in Alzheimer's disease
Background: Different cerebrospinal fluid (CSF) amyloid-beta 1-42 (Aβ1-42), 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 Aβ1-42, 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 Aβ1-42, 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 Aβ1-42, 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 Aβ1-42. 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.
|Persistent URL||dx.doi.org/10.1258/acb.2009.008232, hdl.handle.net/1765/32714|
Verwey, N.A, van der Flier, W.M, Blennow, K, Clark, C, Sokolow, S, de Deyn, P.P, … 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. doi:10.1258/acb.2009.008232