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

This version was published on 1 May 2009

Ann Clin Biochem 2009;46:235-240
© 2009 Association for Clinical Biochemistry


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Original Articles

N A Verwey1,2,
W M van der Flier2,
K Blennow3,
C Clark4,
S Sokolow5,
P P De Deyn6,
D Galasko7,
H Hampel8,9,
T Hartmann10,
E Kapaki11,
L Lannfelt12,
P D Mehta13,
L Parnetti14,
A Petzold15,
T Pirttila16,
L Saleh17,
A Skinningsrud18,
J C v Swieten19,
M M Verbeek20,
J Wiltfang21,
S Younkin22,
P Scheltens2 and
M A Blankenstein1

1 Department of Clinical Chemistry;
2 Department of Neurology, VU University Medical Center, Amsterdam, 1081 HV, The Netherlands;
3 Neurochemistry Lab, Möldal Hospital, Möldal, SE-431 80, Sweden;
4 The Penn Ralston Center, University of Pennsylvania, 19104, Philadelphia;
5 UCLA School of Nursing, Los Angeles, CA 90095, USA;
6 Instituut Born-Bunge, University of Antwerp, Antwerp, BE-2610, Belgium;
7 Department of Biochemical Research, University of San Diego, La Jolla, CA 92093, USA;
8 Department of Psychiatry, Alzheimer Memorial Center, University of Munich, München, D-80336, Germany;
9 Department of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College, Dublin 2, Ireland;
10 Molecular Biology, University of Heidelberg, Heidelberg 69120, Germany;
11 Department of Neurology, Eginition Hospital, Athene, 11528, Greece;
12 Department for Public Health/Geriatrics, Uppsala University, Uppsala 751 25, Sweden;
13 Institute for Basic Research in Development Disabilities, New York 10314, USA;
14 Department of Neurology, Ospedale S.M. della Misericordia, Perugia 06122, Italy;
15 Institute of Neurology, Clinical Neurosciences, UCL, London, WC1N 3BG, UK;
16 Department of Neurology, University of Kuopio, 70210 Kuopio, Finland;
17 Unilabs, CH-8021 Zurich, Switzerland;
18 Department of Clinical Chemistry, Akerhus University Hospital, Lorenskog, NO-1478, Norway;
19 Department of Neurology, Erasmus Medical Center, 3015 CE, Rotterdam;
20 Laboratory of Pediatrics and Neurology, Department of Neurology, Radboud University Nijmegen Medical Centre, Donders Centre for Neuroscience, Alzheimer Center, Nijmegen, 6500 HB, The Netherlands;
21 Neurobiology Laboratory, University of Erlangen-Neurenberg, Erlangen, D-91054, Germany;
22 Mayo Clinic, Jacksonville, FL 32092, USA

Corresponding author: NA Verwey, MD, Department of Clinical Chemistry and Neurology, VU University Medical Center, P.O. BOX 7057, Amsterdam 1007 MB, The Netherlands. Email: n.verwey{at}vumc.nl

Background: Different cerebrospinal fluid (CSF) amyloid-beta 1–42 (Aβ1–42), total Tau (Tau) and Tau phosphorylatedat threonine 181 (P-Tau) levels are reported, but currentlythere is a lack of quality control programmes. The aim of thisstudy was to compare the measurements of these CSF biomarkers,between and within centres.

Methods: Three CSF-pool samples were distributed to 13 laboratories in 2004 and the same samples were 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 ofthese marker(s) by enzyme-linked immunosorbent assays (ELISAs).In 2008, 12 laboratories measured all three markers, three laboratoriesmeasured one or two marker(s) by ELISAs and three laboratoriesmeasured 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 Innotest® (N = 13) for Aβ1–42, lower interCV were calculated (22%). The centres that participated in both years (N = 9) showed interCVsof 21%, 15% and 9% and intra-centre coefficients (intraCV) ofvariance of 25%,18% and 7% in 2008.

Conclusions: The highest variability was found for Aβ1–42. Thevariabilities for Tau and P-Tau were lower in both years. Thecentres that participated in both years showed a high intraCVcomparable to their interCV, indicating that there is not onlya high variation between but also within centres. Besides auniform standardization of (pre)analytical procedures, the sameassay should be used to decrease the inter/intracentre variation.

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