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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">CSF biomarker variability in the Alzheimer’s Association quality control program</title><author><name sortKey="Mattsson, Niklas" sort="Mattsson, Niklas" uniqKey="Mattsson N" first="Niklas" last="Mattsson">Niklas Mattsson</name><affiliation><nlm:aff id="A1">Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="A2">San Francisco VA Medical Center, Center for Imaging of Neurodegenerative Diseases, University of California San Francisco, San Francisco, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Andreasson, Ulf" sort="Andreasson, Ulf" uniqKey="Andreasson U" first="Ulf" last="Andreasson">Ulf Andreasson</name><affiliation><nlm:aff id="A1">Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden</nlm:aff></affiliation></author><author><name sortKey="Persson, Staffan" sort="Persson, Staffan" uniqKey="Persson S" first="Staffan" last="Persson">Staffan Persson</name><affiliation><nlm:aff id="A1">Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden</nlm:aff></affiliation></author><author><name sortKey="Carrillo, Maria C" sort="Carrillo, Maria C" uniqKey="Carrillo M" first="Maria C." last="Carrillo">Maria C. Carrillo</name><affiliation><nlm:aff id="A3">The Alzheimer’s Association, Chicago, IL, USA</nlm:aff></affiliation></author><author><name sortKey="Collins, Steven" sort="Collins, Steven" uniqKey="Collins S" first="Steven" last="Collins">Steven Collins</name><affiliation><nlm:aff id="A4">Department of Pathology, Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Chalbot, Sonia" sort="Chalbot, Sonia" uniqKey="Chalbot S" first="Sonia" last="Chalbot">Sonia Chalbot</name><affiliation><nlm:aff id="A5">New York State Institute for Basic Research, Staten Island, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Cutler, Neal" sort="Cutler, Neal" uniqKey="Cutler N" first="Neal" last="Cutler">Neal Cutler</name><affiliation><nlm:aff id="A6">Worldwide Clinical Trials, Beverly Hills, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Dufour Rainfray, Diane" sort="Dufour Rainfray, Diane" uniqKey="Dufour Rainfray D" first="Diane" last="Dufour-Rainfray">Diane Dufour-Rainfray</name><affiliation><nlm:aff id="A7">CHRU de Tours, Laboratoire de médecine nucléaire; Université François-Rabelais de Tours, PRES Centre-Val de Loire Université; and UMR INSERM U 930 Imagerie et cerveau, Université François-Rabelais de Tours, PRES Centre-Val de Loire Université, Tours, France</nlm:aff></affiliation></author><author><name sortKey="Fagan, Anne M" sort="Fagan, Anne M" uniqKey="Fagan A" first="Anne M." last="Fagan">Anne M. Fagan</name><affiliation><nlm:aff id="A8">Washington University, St. Louis, MO, USA</nlm:aff></affiliation></author><author><name sortKey="Heegaard, Niels H H" sort="Heegaard, Niels H H" uniqKey="Heegaard N" first="Niels H. H." last="Heegaard">Niels H. H. Heegaard</name><affiliation><nlm:aff id="A9">Department of Clinical Biochemistry, Immunology & Genetics, Statens Serum Institut, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Hsiung, Ging Yuek Robin" sort="Hsiung, Ging Yuek Robin" uniqKey="Hsiung G" first="Ging-Yuek Robin" last="Hsiung">Ging-Yuek Robin Hsiung</name><affiliation><nlm:aff id="A10">University of British Columbia, Vancouver, Canada</nlm:aff></affiliation></author><author><name sortKey="Hyman, Bradley" sort="Hyman, Bradley" uniqKey="Hyman B" first="Bradley" last="Hyman">Bradley Hyman</name><affiliation><nlm:aff id="A11">MassGeneral Institute for Neurodegenerative Disease, Charlestown, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Iqbal, Khalid" sort="Iqbal, Khalid" uniqKey="Iqbal K" first="Khalid" last="Iqbal">Khalid Iqbal</name><affiliation><nlm:aff id="A5">New York State Institute for Basic Research, Staten Island, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Lachno, D Richard" sort="Lachno, D Richard" uniqKey="Lachno D" first="D. Richard" last="Lachno">D. Richard Lachno</name><affiliation><nlm:aff id="A12">Eli Lilly and Company, Windlesham, UK</nlm:aff></affiliation></author><author><name sortKey="Lle, Alberto" sort="Lle, Alberto" uniqKey="Lle A" first="Alberto" last="Lle">Alberto Lle</name><affiliation><nlm:aff id="A13">Hospital de Sant Pau, Barcelona, Spain</nlm:aff></affiliation></author><author><name sortKey="Lewczuk, Piotr" sort="Lewczuk, Piotr" uniqKey="Lewczuk P" first="Piotr" last="Lewczuk">Piotr Lewczuk</name><affiliation><nlm:aff id="A14">Universitätsklinikum Erlangen, Erlangen, Germany</nlm:aff></affiliation></author><author><name sortKey="Molinuevo, Jose L" sort="Molinuevo, Jose L" uniqKey="Molinuevo J" first="José L." last="Molinuevo">José L. Molinuevo</name><affiliation><nlm:aff id="A15">Alzheimer’s Disease and Other Cognitive Disorders Unit, Neurology Service, ICN Hospital Clinic i Universitari and Pasqual Maragall Foundation, Barcelona, Spain</nlm:aff></affiliation></author><author><name sortKey="Parchi, Piero" sort="Parchi, Piero" uniqKey="Parchi P" first="Piero" last="Parchi">Piero Parchi</name><affiliation><nlm:aff id="A16">Institute of Neurological Sciences and Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy</nlm:aff></affiliation></author><author><name sortKey="Regeniter, Axel" sort="Regeniter, Axel" uniqKey="Regeniter A" first="Axel" last="Regeniter">Axel Regeniter</name><affiliation><nlm:aff id="A17">Basel University Hospital, Basel, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Rissman, Robert" sort="Rissman, Robert" uniqKey="Rissman R" first="Robert" last="Rissman">Robert Rissman</name><affiliation><nlm:aff id="A18">School of Medicine, University California, San Diego, La Jolla, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Rosenmann, Hanna" sort="Rosenmann, Hanna" uniqKey="Rosenmann H" first="Hanna" last="Rosenmann">Hanna Rosenmann</name><affiliation><nlm:aff id="A19">Hadassah Hebrew University Medical Center, Jerusalem, Israel</nlm:aff></affiliation></author><author><name sortKey="Sancesario, Giuseppe" sort="Sancesario, Giuseppe" uniqKey="Sancesario G" first="Giuseppe" last="Sancesario">Giuseppe Sancesario</name><affiliation><nlm:aff id="A20">General Hospital of University of Rome Tor Vergata, Rome, Italy</nlm:aff></affiliation></author><author><name sortKey="Schroder, Johannes" sort="Schroder, Johannes" uniqKey="Schroder J" first="Johannes" last="Schröder">Johannes Schröder</name><affiliation><nlm:aff id="A21">Sektion Gerontopsychiatrie Universitätsklinikum, Heidelberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Shaw, Leslie M" sort="Shaw, Leslie M" uniqKey="Shaw L" first="Leslie M." last="Shaw">Leslie M. Shaw</name><affiliation><nlm:aff id="A22">University of Pennsylvania, Philadelphia, PA, USA</nlm:aff></affiliation></author><author><name sortKey="Teunissen, Charlotte E" sort="Teunissen, Charlotte E" uniqKey="Teunissen C" first="Charlotte E." last="Teunissen">Charlotte E. Teunissen</name><affiliation><nlm:aff id="A23">Department of Clinical Chemistry, VU University Medical Center, Amsterdam, Netherlands</nlm:aff></affiliation></author><author><name sortKey="Trojanowski, John Q" sort="Trojanowski, John Q" uniqKey="Trojanowski J" first="John Q." last="Trojanowski">John Q. Trojanowski</name><affiliation><nlm:aff id="A22">University of Pennsylvania, Philadelphia, PA, USA</nlm:aff></affiliation></author><author><name sortKey="Vanderstichele, Hugo" sort="Vanderstichele, Hugo" uniqKey="Vanderstichele H" first="Hugo" last="Vanderstichele">Hugo Vanderstichele</name><affiliation><nlm:aff id="A24">ADx NeuroSciences, Gent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Vandijck, Manu" sort="Vandijck, Manu" uniqKey="Vandijck M" first="Manu" last="Vandijck">Manu Vandijck</name><affiliation><nlm:aff id="A25">Innogenetics nv (part of Fujirebio), Gent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Verbeek, Marcel M" sort="Verbeek, Marcel M" uniqKey="Verbeek M" first="Marcel M." last="Verbeek">Marcel M. Verbeek</name><affiliation><nlm:aff id="A26">Departments of Neurology and Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, Netherlands</nlm:aff></affiliation></author><author><name sortKey="Zetterberg, Henrik" sort="Zetterberg, Henrik" uniqKey="Zetterberg H" first="Henrik" last="Zetterberg">Henrik Zetterberg</name><affiliation><nlm:aff id="A1">Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="A27">Institute of Neurology, University College London, Queen Square, London, UK</nlm:aff></affiliation></author><author><name sortKey="Blennow, Kaj" sort="Blennow, Kaj" uniqKey="Blennow K" first="Kaj" last="Blennow">Kaj Blennow</name><affiliation><nlm:aff id="A1">Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden</nlm:aff></affiliation></author><author><name sortKey="K Ser, Stephan A" sort="K Ser, Stephan A" uniqKey="K Ser S" first="Stephan A." last="K Ser">Stephan A. K Ser</name><affiliation><nlm:aff id="A28">University of Tübingen, Tübingen, Germany</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23622690</idno><idno type="pmc">3707386</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3707386</idno><idno type="RBID">PMC:3707386</idno><idno type="doi">10.1016/j.jalz.2013.01.010</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">001E23</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001E23</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">CSF biomarker variability in the Alzheimer’s Association quality control program</title><author><name sortKey="Mattsson, Niklas" sort="Mattsson, Niklas" uniqKey="Mattsson N" first="Niklas" last="Mattsson">Niklas Mattsson</name><affiliation><nlm:aff id="A1">Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="A2">San Francisco VA Medical Center, Center for Imaging of Neurodegenerative Diseases, University of California San Francisco, San Francisco, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Andreasson, Ulf" sort="Andreasson, Ulf" uniqKey="Andreasson U" first="Ulf" last="Andreasson">Ulf Andreasson</name><affiliation><nlm:aff id="A1">Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden</nlm:aff></affiliation></author><author><name sortKey="Persson, Staffan" sort="Persson, Staffan" uniqKey="Persson S" first="Staffan" last="Persson">Staffan Persson</name><affiliation><nlm:aff id="A1">Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden</nlm:aff></affiliation></author><author><name sortKey="Carrillo, Maria C" sort="Carrillo, Maria C" uniqKey="Carrillo M" first="Maria C." last="Carrillo">Maria C. Carrillo</name><affiliation><nlm:aff id="A3">The Alzheimer’s Association, Chicago, IL, USA</nlm:aff></affiliation></author><author><name sortKey="Collins, Steven" sort="Collins, Steven" uniqKey="Collins S" first="Steven" last="Collins">Steven Collins</name><affiliation><nlm:aff id="A4">Department of Pathology, Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Chalbot, Sonia" sort="Chalbot, Sonia" uniqKey="Chalbot S" first="Sonia" last="Chalbot">Sonia Chalbot</name><affiliation><nlm:aff id="A5">New York State Institute for Basic Research, Staten Island, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Cutler, Neal" sort="Cutler, Neal" uniqKey="Cutler N" first="Neal" last="Cutler">Neal Cutler</name><affiliation><nlm:aff id="A6">Worldwide Clinical Trials, Beverly Hills, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Dufour Rainfray, Diane" sort="Dufour Rainfray, Diane" uniqKey="Dufour Rainfray D" first="Diane" last="Dufour-Rainfray">Diane Dufour-Rainfray</name><affiliation><nlm:aff id="A7">CHRU de Tours, Laboratoire de médecine nucléaire; Université François-Rabelais de Tours, PRES Centre-Val de Loire Université; and UMR INSERM U 930 Imagerie et cerveau, Université François-Rabelais de Tours, PRES Centre-Val de Loire Université, Tours, France</nlm:aff></affiliation></author><author><name sortKey="Fagan, Anne M" sort="Fagan, Anne M" uniqKey="Fagan A" first="Anne M." last="Fagan">Anne M. Fagan</name><affiliation><nlm:aff id="A8">Washington University, St. Louis, MO, USA</nlm:aff></affiliation></author><author><name sortKey="Heegaard, Niels H H" sort="Heegaard, Niels H H" uniqKey="Heegaard N" first="Niels H. H." last="Heegaard">Niels H. H. Heegaard</name><affiliation><nlm:aff id="A9">Department of Clinical Biochemistry, Immunology & Genetics, Statens Serum Institut, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Hsiung, Ging Yuek Robin" sort="Hsiung, Ging Yuek Robin" uniqKey="Hsiung G" first="Ging-Yuek Robin" last="Hsiung">Ging-Yuek Robin Hsiung</name><affiliation><nlm:aff id="A10">University of British Columbia, Vancouver, Canada</nlm:aff></affiliation></author><author><name sortKey="Hyman, Bradley" sort="Hyman, Bradley" uniqKey="Hyman B" first="Bradley" last="Hyman">Bradley Hyman</name><affiliation><nlm:aff id="A11">MassGeneral Institute for Neurodegenerative Disease, Charlestown, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Iqbal, Khalid" sort="Iqbal, Khalid" uniqKey="Iqbal K" first="Khalid" last="Iqbal">Khalid Iqbal</name><affiliation><nlm:aff id="A5">New York State Institute for Basic Research, Staten Island, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Lachno, D Richard" sort="Lachno, D Richard" uniqKey="Lachno D" first="D. Richard" last="Lachno">D. Richard Lachno</name><affiliation><nlm:aff id="A12">Eli Lilly and Company, Windlesham, UK</nlm:aff></affiliation></author><author><name sortKey="Lle, Alberto" sort="Lle, Alberto" uniqKey="Lle A" first="Alberto" last="Lle">Alberto Lle</name><affiliation><nlm:aff id="A13">Hospital de Sant Pau, Barcelona, Spain</nlm:aff></affiliation></author><author><name sortKey="Lewczuk, Piotr" sort="Lewczuk, Piotr" uniqKey="Lewczuk P" first="Piotr" last="Lewczuk">Piotr Lewczuk</name><affiliation><nlm:aff id="A14">Universitätsklinikum Erlangen, Erlangen, Germany</nlm:aff></affiliation></author><author><name sortKey="Molinuevo, Jose L" sort="Molinuevo, Jose L" uniqKey="Molinuevo J" first="José L." last="Molinuevo">José L. Molinuevo</name><affiliation><nlm:aff id="A15">Alzheimer’s Disease and Other Cognitive Disorders Unit, Neurology Service, ICN Hospital Clinic i Universitari and Pasqual Maragall Foundation, Barcelona, Spain</nlm:aff></affiliation></author><author><name sortKey="Parchi, Piero" sort="Parchi, Piero" uniqKey="Parchi P" first="Piero" last="Parchi">Piero Parchi</name><affiliation><nlm:aff id="A16">Institute of Neurological Sciences and Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy</nlm:aff></affiliation></author><author><name sortKey="Regeniter, Axel" sort="Regeniter, Axel" uniqKey="Regeniter A" first="Axel" last="Regeniter">Axel Regeniter</name><affiliation><nlm:aff id="A17">Basel University Hospital, Basel, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Rissman, Robert" sort="Rissman, Robert" uniqKey="Rissman R" first="Robert" last="Rissman">Robert Rissman</name><affiliation><nlm:aff id="A18">School of Medicine, University California, San Diego, La Jolla, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Rosenmann, Hanna" sort="Rosenmann, Hanna" uniqKey="Rosenmann H" first="Hanna" last="Rosenmann">Hanna Rosenmann</name><affiliation><nlm:aff id="A19">Hadassah Hebrew University Medical Center, Jerusalem, Israel</nlm:aff></affiliation></author><author><name sortKey="Sancesario, Giuseppe" sort="Sancesario, Giuseppe" uniqKey="Sancesario G" first="Giuseppe" last="Sancesario">Giuseppe Sancesario</name><affiliation><nlm:aff id="A20">General Hospital of University of Rome Tor Vergata, Rome, Italy</nlm:aff></affiliation></author><author><name sortKey="Schroder, Johannes" sort="Schroder, Johannes" uniqKey="Schroder J" first="Johannes" last="Schröder">Johannes Schröder</name><affiliation><nlm:aff id="A21">Sektion Gerontopsychiatrie Universitätsklinikum, Heidelberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Shaw, Leslie M" sort="Shaw, Leslie M" uniqKey="Shaw L" first="Leslie M." last="Shaw">Leslie M. Shaw</name><affiliation><nlm:aff id="A22">University of Pennsylvania, Philadelphia, PA, USA</nlm:aff></affiliation></author><author><name sortKey="Teunissen, Charlotte E" sort="Teunissen, Charlotte E" uniqKey="Teunissen C" first="Charlotte E." last="Teunissen">Charlotte E. Teunissen</name><affiliation><nlm:aff id="A23">Department of Clinical Chemistry, VU University Medical Center, Amsterdam, Netherlands</nlm:aff></affiliation></author><author><name sortKey="Trojanowski, John Q" sort="Trojanowski, John Q" uniqKey="Trojanowski J" first="John Q." last="Trojanowski">John Q. Trojanowski</name><affiliation><nlm:aff id="A22">University of Pennsylvania, Philadelphia, PA, USA</nlm:aff></affiliation></author><author><name sortKey="Vanderstichele, Hugo" sort="Vanderstichele, Hugo" uniqKey="Vanderstichele H" first="Hugo" last="Vanderstichele">Hugo Vanderstichele</name><affiliation><nlm:aff id="A24">ADx NeuroSciences, Gent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Vandijck, Manu" sort="Vandijck, Manu" uniqKey="Vandijck M" first="Manu" last="Vandijck">Manu Vandijck</name><affiliation><nlm:aff id="A25">Innogenetics nv (part of Fujirebio), Gent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Verbeek, Marcel M" sort="Verbeek, Marcel M" uniqKey="Verbeek M" first="Marcel M." last="Verbeek">Marcel M. Verbeek</name><affiliation><nlm:aff id="A26">Departments of Neurology and Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, Netherlands</nlm:aff></affiliation></author><author><name sortKey="Zetterberg, Henrik" sort="Zetterberg, Henrik" uniqKey="Zetterberg H" first="Henrik" last="Zetterberg">Henrik Zetterberg</name><affiliation><nlm:aff id="A1">Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="A27">Institute of Neurology, University College London, Queen Square, London, UK</nlm:aff></affiliation></author><author><name sortKey="Blennow, Kaj" sort="Blennow, Kaj" uniqKey="Blennow K" first="Kaj" last="Blennow">Kaj Blennow</name><affiliation><nlm:aff id="A1">Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden</nlm:aff></affiliation></author><author><name sortKey="K Ser, Stephan A" sort="K Ser, Stephan A" uniqKey="K Ser S" first="Stephan A." last="K Ser">Stephan A. K Ser</name><affiliation><nlm:aff id="A28">University of Tübingen, Tübingen, Germany</nlm:aff></affiliation></author></analytic><series><title level="j">Alzheimer's & dementia : the journal of the Alzheimer's Association</title><idno type="ISSN">1552-5260</idno><idno type="eISSN">1552-5279</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background</title><p id="P1">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.</p></sec><sec id="S2"><title>Methods</title><p id="P2">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 (Mölndal, Sweden) were analyzed by single-analyte enzyme-linked immunosorbent assay (ELISA), a multiplexing xMAP assay, or an immunoassay with electrochemoluminescence detection.</p></sec><sec id="S3"><title>Results</title><p id="P3">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).</p></sec><sec id="S4"><title>Conclusions</title><p id="P4">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.</p></sec></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
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<front><journal-meta><journal-id journal-id-type="nlm-journal-id">101231978</journal-id><journal-id journal-id-type="pubmed-jr-id">33173</journal-id><journal-id journal-id-type="nlm-ta">Alzheimers Dement</journal-id><journal-id journal-id-type="iso-abbrev">Alzheimers Dement</journal-id><journal-title-group><journal-title>Alzheimer's & dementia : the journal of the Alzheimer's Association</journal-title></journal-title-group><issn pub-type="ppub">1552-5260</issn><issn pub-type="epub">1552-5279</issn></journal-meta><article-meta><article-id pub-id-type="pmid">23622690</article-id><article-id pub-id-type="pmc">3707386</article-id><article-id pub-id-type="doi">10.1016/j.jalz.2013.01.010</article-id><article-id pub-id-type="manuscript">NIHMS487510</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>CSF biomarker variability in the Alzheimer’s Association quality control program</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Mattsson</surname><given-names>Niklas</given-names></name><xref ref-type="aff" rid="A1">a</xref><xref ref-type="aff" rid="A2">b</xref><xref rid="FN1" ref-type="author-notes">*</xref></contrib><contrib contrib-type="author"><name><surname>Andreasson</surname><given-names>Ulf</given-names></name><xref ref-type="aff" rid="A1">a</xref></contrib><contrib contrib-type="author"><name><surname>Persson</surname><given-names>Staffan</given-names></name><xref ref-type="aff" rid="A1">a</xref></contrib><contrib contrib-type="author"><name><surname>Carrillo</surname><given-names>Maria C.</given-names></name><xref ref-type="aff" rid="A3">c</xref></contrib><contrib contrib-type="author"><name><surname>Collins</surname><given-names>Steven</given-names></name><xref ref-type="aff" rid="A4">d</xref></contrib><contrib contrib-type="author"><name><surname>Chalbot</surname><given-names>Sonia</given-names></name><xref ref-type="aff" rid="A5">e</xref></contrib><contrib contrib-type="author"><name><surname>Cutler</surname><given-names>Neal</given-names></name><xref ref-type="aff" rid="A6">f</xref></contrib><contrib contrib-type="author"><name><surname>Dufour-Rainfray</surname><given-names>Diane</given-names></name><xref ref-type="aff" rid="A7">g</xref></contrib><contrib contrib-type="author"><name><surname>Fagan</surname><given-names>Anne M.</given-names></name><xref ref-type="aff" rid="A8">h</xref></contrib><contrib contrib-type="author"><name><surname>Heegaard</surname><given-names>Niels H. H.</given-names></name><xref ref-type="aff" rid="A9">i</xref></contrib><contrib contrib-type="author"><name><surname>Hsiung</surname><given-names>Ging-Yuek Robin</given-names></name><xref ref-type="aff" rid="A10">j</xref></contrib><contrib contrib-type="author"><name><surname>Hyman</surname><given-names>Bradley</given-names></name><xref ref-type="aff" rid="A11">k</xref></contrib><contrib contrib-type="author"><name><surname>Iqbal</surname><given-names>Khalid</given-names></name><xref ref-type="aff" rid="A5">e</xref></contrib><contrib contrib-type="author"><name><surname>Lachno</surname><given-names>D. Richard</given-names></name><xref ref-type="aff" rid="A12">l</xref></contrib><contrib contrib-type="author"><name><surname>Lleó</surname><given-names>Alberto</given-names></name><xref ref-type="aff" rid="A13">m</xref></contrib><contrib contrib-type="author"><name><surname>Lewczuk</surname><given-names>Piotr</given-names></name><xref ref-type="aff" rid="A14">n</xref></contrib><contrib contrib-type="author"><name><surname>Molinuevo</surname><given-names>José L.</given-names></name><xref ref-type="aff" rid="A15">o</xref></contrib><contrib contrib-type="author"><name><surname>Parchi</surname><given-names>Piero</given-names></name><xref ref-type="aff" rid="A16">p</xref></contrib><contrib contrib-type="author"><name><surname>Regeniter</surname><given-names>Axel</given-names></name><xref ref-type="aff" rid="A17">q</xref></contrib><contrib contrib-type="author"><name><surname>Rissman</surname><given-names>Robert</given-names></name><xref ref-type="aff" rid="A18">r</xref></contrib><contrib contrib-type="author"><name><surname>Rosenmann</surname><given-names>Hanna</given-names></name><xref ref-type="aff" rid="A19">s</xref></contrib><contrib contrib-type="author"><name><surname>Sancesario</surname><given-names>Giuseppe</given-names></name><xref ref-type="aff" rid="A20">t</xref></contrib><contrib contrib-type="author"><name><surname>Schröder</surname><given-names>Johannes</given-names></name><xref ref-type="aff" rid="A21">u</xref></contrib><contrib contrib-type="author"><name><surname>Shaw</surname><given-names>Leslie M.</given-names></name><xref ref-type="aff" rid="A22">v</xref></contrib><contrib contrib-type="author"><name><surname>Teunissen</surname><given-names>Charlotte E.</given-names></name><xref ref-type="aff" rid="A23">w</xref></contrib><contrib contrib-type="author"><name><surname>Trojanowski</surname><given-names>John Q.</given-names></name><xref ref-type="aff" rid="A22">v</xref></contrib><contrib contrib-type="author"><name><surname>Vanderstichele</surname><given-names>Hugo</given-names></name><xref ref-type="aff" rid="A24">x</xref></contrib><contrib contrib-type="author"><name><surname>Vandijck</surname><given-names>Manu</given-names></name><xref ref-type="aff" rid="A25">y</xref></contrib><contrib contrib-type="author"><name><surname>Verbeek</surname><given-names>Marcel M.</given-names></name><xref ref-type="aff" rid="A26">z</xref></contrib><contrib contrib-type="author"><name><surname>Zetterberg</surname><given-names>Henrik</given-names></name><xref ref-type="aff" rid="A1">a</xref><xref ref-type="aff" rid="A27">aa</xref></contrib><contrib contrib-type="author"><name><surname>Blennow</surname><given-names>Kaj</given-names></name><xref ref-type="aff" rid="A1">a</xref></contrib><contrib contrib-type="author"><name><surname>Käser</surname><given-names>Stephan A.</given-names></name><xref ref-type="aff" rid="A28">bb</xref></contrib><on-behalf-of>on behalf of the Alzheimer’s Association QC Program Work Group</on-behalf-of></contrib-group><aff id="A1"><label>a</label>Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden</aff><aff id="A2"><label>b</label>San Francisco VA Medical Center, Center for Imaging of Neurodegenerative Diseases, University of California San Francisco, San Francisco, CA, USA</aff><aff id="A3"><label>c</label>The Alzheimer’s Association, Chicago, IL, USA</aff><aff id="A4"><label>d</label>Department of Pathology, Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Australia</aff><aff id="A5"><label>e</label>New York State Institute for Basic Research, Staten Island, NY, USA</aff><aff id="A6"><label>f</label>Worldwide Clinical Trials, Beverly Hills, CA, USA</aff><aff id="A7"><label>g</label>CHRU de Tours, Laboratoire de médecine nucléaire; Université François-Rabelais de Tours, PRES Centre-Val de Loire Université; and UMR INSERM U 930 Imagerie et cerveau, Université François-Rabelais de Tours, PRES Centre-Val de Loire Université, Tours, France</aff><aff id="A8"><label>h</label>Washington University, St. Louis, MO, USA</aff><aff id="A9"><label>i</label>Department of Clinical Biochemistry, Immunology & Genetics, Statens Serum Institut, Copenhagen, Denmark</aff><aff id="A10"><label>j</label>University of British Columbia, Vancouver, Canada</aff><aff id="A11"><label>k</label>MassGeneral Institute for Neurodegenerative Disease, Charlestown, MA, USA</aff><aff id="A12"><label>l</label>Eli Lilly and Company, Windlesham, UK</aff><aff id="A13"><label>m</label>Hospital de Sant Pau, Barcelona, Spain</aff><aff id="A14"><label>n</label>Universitätsklinikum Erlangen, Erlangen, Germany</aff><aff id="A15"><label>o</label>Alzheimer’s Disease and Other Cognitive Disorders Unit, Neurology Service, ICN Hospital Clinic i Universitari and Pasqual Maragall Foundation, Barcelona, Spain</aff><aff id="A16"><label>p</label>Institute of Neurological Sciences and Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy</aff><aff id="A17"><label>q</label>Basel University Hospital, Basel, Switzerland</aff><aff id="A18"><label>r</label>School of Medicine, University California, San Diego, La Jolla, CA, USA</aff><aff id="A19"><label>s</label>Hadassah Hebrew University Medical Center, Jerusalem, Israel</aff><aff id="A20"><label>t</label>General Hospital of University of Rome Tor Vergata, Rome, Italy</aff><aff id="A21"><label>u</label>Sektion Gerontopsychiatrie Universitätsklinikum, Heidelberg, Germany</aff><aff id="A22"><label>v</label>University of Pennsylvania, Philadelphia, PA, USA</aff><aff id="A23"><label>w</label>Department of Clinical Chemistry, VU University Medical Center, Amsterdam, Netherlands</aff><aff id="A24"><label>x</label>ADx NeuroSciences, Gent, Belgium</aff><aff id="A25"><label>y</label>Innogenetics nv (part of Fujirebio), Gent, Belgium</aff><aff id="A26"><label>z</label>Departments of Neurology and Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, Netherlands</aff><aff id="A27"><label>aa</label>Institute of Neurology, University College London, Queen Square, London, UK</aff><aff id="A28"><label>bb</label>University of Tübingen, Tübingen, Germany</aff><author-notes><corresp id="FN1"><label>*</label>Corresponding author. Tel.: +1-415-494-1139; Fax: +1-415-668-2864. <email>niklas.mattsson@neuro.gu.se</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>20</day><month>6</month><year>2013</year></pub-date><pub-date pub-type="ppub"><month>5</month><year>2013</year></pub-date><pub-date pub-type="pmc-release"><day>01</day><month>5</month><year>2014</year></pub-date><volume>9</volume><issue>3</issue><fpage>251</fpage><lpage>261</lpage><permissions><copyright-statement>© 2013 The Alzheimer’s Association. All rights reserved.</copyright-statement><copyright-year>2013</copyright-year></permissions><abstract><sec id="S1"><title>Background</title><p id="P1">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.</p></sec><sec id="S2"><title>Methods</title><p id="P2">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 (Mölndal, Sweden) were analyzed by single-analyte enzyme-linked immunosorbent assay (ELISA), a multiplexing xMAP assay, or an immunoassay with electrochemoluminescence detection.</p></sec><sec id="S3"><title>Results</title><p id="P3">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).</p></sec><sec id="S4"><title>Conclusions</title><p id="P4">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.</p></sec></abstract><kwd-group><kwd>Alzheimer’s disease</kwd><kwd>Cerebrospinal fluid</kwd><kwd>Biomarkers</kwd><kwd>External assurance</kwd><kwd>Quality control</kwd><kwd>Proficiency testing</kwd></kwd-group><funding-group><award-group><funding-source country="United States">National Institute on Aging : NIA</funding-source><award-id>P50 AG005134 || AG</award-id></award-group></funding-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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