CSF biomarker variability in the Alzheimer's Association quality control program
Por:
Mattsson, N, Andreasson, U, Persson, S, Carrillo, MC, Collins, S, Chalbot, S, Cutler, N, Dufour-Rainfray, D, Fagan, AM, Heegaard, NHH, Hsiung, GYR, Hyman, B, Iqbal, K, Lachno, DR, Lleo, A, Lewczuk, P, Molinuevo, JL, Parchi, P, Regeniter, A, Rissman, R, Rosenmann, H, Sancesario, G, Schroder, J, Shaw, LM, Teunissen, CE, Trojanowski, JQ, Vanderstichele, H, Vandijck, M, Verbeek, MM, Zetterberg, H, Blennow, K, Kaser, SA
Publicada:
1 may 2013
Resumen:
Background: The cerebrospinal fluid (CSF) biomarkers amyloid beta 1-42, total tau, and phosphorylated tau are used increasingly for Alzheimer's disease (AD) research and patient management. However, there are large variations in biomarker measurements among and within laboratories.
Methods: Data from the first nine rounds of the Alzheimer's Association quality control program was used to define the extent and sources of analytical variability. In each round, three CSF samples prepared at the Clinical Neurochemistry Laboratory (Molndal, Sweden) were analyzed by single-analyte enzyme-linked immunosorbent assay (ELISA), a multiplexing xMAP assay, or an immunoassay with electrochemoluminescence detection.
Results: A total of 84 laboratories participated. Coefficients of variation (CVs) between laboratories were around 20% to 30%; within-run CVs, less than 5% to 10%; and longitudinal within-laboratory CVs, 5% to 19%. Interestingly, longitudinal within-laboratory CV differed between biomarkers at individual laboratories, suggesting that a component of it was assay dependent. Variability between kit lots and between laboratories both had a major influence on amyloid beta 1-42 measurements, but for total tau and phosphorylated tau, between-kit lot effects were much less than between-laboratory effects. Despite the measurement variability, the between-laboratory consistency in classification of samples (using prehoc-derived cutoffs for AD) was high (>90% in 15 of 18 samples for ELISA and in 12 of 18 samples for xMAP).
Conclusions: The overall variability remains too high to allow assignment of universal biomarker cutoff values for a specific intended use. Each laboratory must ensure longitudinal stability in its measurements and use internally qualified cutoff levels. Further standardization of laboratory procedures and improvement of kit performance will likely increase the usefulness of CSF AD biomarkers for researchers and clinicians. (C) 2013 The Alzheimer's Association. All rights reserved.
Filiaciones:
Mattsson, N:
Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad,Inst Neurosci & Physiol, Clin Neurochem Lab,Dept Psychiat & Neurochem, Molndal, Sweden
Univ Calif San Francisco, San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94143 USA
Andreasson, U:
Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad,Inst Neurosci & Physiol, Clin Neurochem Lab,Dept Psychiat & Neurochem, Molndal, Sweden
Persson, S:
Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad,Inst Neurosci & Physiol, Clin Neurochem Lab,Dept Psychiat & Neurochem, Molndal, Sweden
Carrillo, MC:
Alzheinzers Assoc, Chicago, IL USA
Collins, S:
Univ Melbourne, Dept Pathol, Florey Inst Neurosci & Mental Hlth, Melbourne, Vic, Australia
Chalbot, S:
New York State Inst Basic Res, Staten Isl, NY USA
Cutler, N:
Worldwide Clin Trials, Beverly Hills, CA USA
Dufour-Rainfray, D:
CHRU Tours, Nucl Med Lab, Tours, France
Univ Tours, Val Loire Univ, PRES Ctr, Tours, France
Univ Tours, Val Loire Univ, PRES Ctr, UMR INSERM Imagerie & Cerveau U930, Tours, France
Fagan, AM:
Washington Univ, St Louis, MO USA
Heegaard, NHH:
Statens Serum Inst, Dept Clin Biochem Immunol & Genet, DK-2300 Copenhagen, Denmark
Hsiung, GYR:
Univ British Columbia, Vancouver, BC V5Z 1M9, Canada
Hyman, B:
MassGen Inst Neurodegenerat Dis, Charlestown, MA USA
Iqbal, K:
New York State Inst Basic Res, Staten Isl, NY USA
Lachno, DR:
Eli Lilly & Co, Windlesham, Surrey, England
Lleo, A:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Lewczuk, P:
Univ Klinikum Erlangen, Erlangen, Germany
Molinuevo, JL:
ICN Hosp Clin & Univ, Neurol Serv, Alzheimers Dis & Other Cognit Disorders Unit, Barcelona, Spain
Pasqual Maragall Fdn, Barcelona, Spain
Parchi, P:
Univ Bologna, Inst Neurol Sci, Bologna, Italy
Univ Bologna, Dept Biomed & Neuromotor Sci, Bologna, Italy
Regeniter, A:
Univ Basel Hosp, CH-4031 Basel, Switzerland
Rissman, R:
Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA
Rosenmann, H:
Hadassah Hebrew Univ, Med Ctr, Jerusalem, Israel
Sancesario, G:
Univ Roma Tor Vergata, Gen Hosp, Rome, Italy
Schroder, J:
Univ Klinikum Heidelberg, Sekt Gerontopsychiat, Heidelberg, Germany
Shaw, LM:
Univ Penn, Philadelphia, PA 19104 USA
Teunissen, CE:
Vrije Univ Amsterdam Med Ctr, Dept Clin Chem, Amsterdam, Netherlands
Trojanowski, JQ:
Univ Penn, Philadelphia, PA 19104 USA
Vanderstichele, H:
ADx NeuroSci, Ghent, Belgium
Vandijck, M:
Innogenet Nv, Ghent, Belgium
Verbeek, MM:
Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain, Dept Neurol, NL-6525 ED Nijmegen, Netherlands
Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain, Dept Lab Med, NL-6525 ED Nijmegen, Netherlands
Zetterberg, H:
Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad,Inst Neurosci & Physiol, Clin Neurochem Lab,Dept Psychiat & Neurochem, Molndal, Sweden
UCL, Inst Neurol, London, England
Blennow, K:
Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad,Inst Neurosci & Physiol, Clin Neurochem Lab,Dept Psychiat & Neurochem, Molndal, Sweden
Kaser, SA:
Univ Tubingen, Tubingen, Germany
Green Accepted, Green Published
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