The World Journal of Biological Psychiatry
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Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry
Piotr Lewczuk, Peter Riederer, Sid E. O’Bryant, Marcel M. Verbeek, Bruno Dubois, Pieter Jelle Visser, Kurt A. Jellinger, Sebastiaan Engelborghs, Alfredo Ramirez, Lucilla Parnetti, Clifford R. Jack Jr, Charlotte E. Teunissen, Harald Hampel, Alberto Lleó, Frank Jessen, Lidia Glodzik, Mony J. de Leon, Anne M. Fagan, José Luis Molinuevo, Willemijn J. Jansen, Bengt Winblad, Leslie M. Shaw, Ulf Andreasson, Markus Otto, Brit Mollenhauer, Jens Wiltfang, Martin R. Turner, Inga Zerr, Ron Handels, Alexander G. Thompson, Gunilla Johansson, Natalia Ermann, John Q. Trojanowski, Ilker Karaca, Holger Wagner, Patrick Oeckl, Linda van Waalwijk van Doorn, Maria Bjerke, Dimitrios Kapogiannis, H. Bea Kuiperij, Lucia Farotti, Yi Li, Brian A. Gordon, Stéphane Epelbaum, Stephanie J. B. Vos, Catharina J. M. Klijn, William E. Van Nostrand, Carolina Minguillon, Matthias Schmitz, Carla Gallo, Andrea Lopez Mato, Florence Thibaut, Simone Lista, Daniel Alcolea, Henrik Zetterberg, Kaj Blennow, Johannes Kornhuber & on Behalf of the Members of the WFSBP Task Force Working on this Topic: Peter Riederer, Carla Gallo, Dimitrios Kapogiannis, Andrea Lopez Mato, Florence Thibaut
To cite this article: Piotr Lewczuk, Peter Riederer, Sid E. O’Bryant, Marcel M. Verbeek, Bruno Dubois, Pieter Jelle Visser, Kurt A. Jellinger, Sebastiaan Engelborghs, Alfredo Ramirez, Lucilla Parnetti, Clifford R. Jack Jr, Charlotte E. Teunissen, Harald Hampel, Alberto Lleó, Frank Jessen, Lidia Glodzik, Mony J. de Leon, Anne M. Fagan, José Luis Molinuevo, Willemijn J. Jansen, Bengt Winblad, Leslie M. Shaw, Ulf Andreasson, Markus Otto, Brit Mollenhauer, Jens Wiltfang, Martin R. Turner, Inga Zerr, Ron Handels, Alexander G. Thompson, Gunilla Johansson, Natalia Ermann, John Q. Trojanowski, Ilker Karaca, Holger Wagner, Patrick Oeckl, Linda van Waalwijk van Doorn, Maria Bjerke, Dimitrios Kapogiannis, H. Bea Kuiperij, Lucia Farotti, Yi Li, Brian A. Gordon, Stéphane Epelbaum, Stephanie J. B. Vos, Catharina J. M. Klijn, William E. Van Nostrand, Carolina Minguillon, Matthias Schmitz, Carla Gallo, Andrea Lopez Mato, Florence Thibaut, Simone Lista, Daniel Alcolea, Henrik Zetterberg, Kaj Blennow, Johannes Kornhuber & on Behalf of the Members of the WFSBP Task Force Working on this Topic: Peter Riederer, Carla Gallo, Dimitrios Kapogiannis, Andrea Lopez Mato, Florence Thibaut (2017): Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry, The World Journal of Biological Psychiatry, DOI: 10.1080/15622975.2017.1375556 To link to this article: http://dx.doi.org/10.1080/15622975.2017.1375556 © 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
Published online: 27 Oct 2017.
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Download by: [the Medical University of Vienna], [Professor Siegfried Kasper] Date: 03 November 2017, At: 06:38 THE WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY, 2017 https://doi.org/10.1080/15622975.2017.1375556
WFSBP CONSENSUS PAPER Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry
Piotr Lewczuka,b , Peter Riedererc, Sid E. O’Bryantd, Marcel M. Verbeeke,f , Bruno Duboisg, Pieter Jelle Visserh,i, Kurt A. Jellingerj, Sebastiaan Engelborghsk,l, Alfredo Ramirezm,n,o , Lucilla Parnettip , Clifford R. Jack Jrq , Charlotte E. Teunissenr, Harald Hampels, Alberto Lleo t,u , Frank Jesseno,v, Lidia Glodzikw, Mony J. de Leonw, Anne M. Faganx,y, Jose Luis Molinuevoz,aa, Willemijn J. Jansenh, Bengt Winbladab, Leslie M. Shawac, Ulf Andreassonad,ae, Markus Ottoaf, Brit Mollenhauerag, Jens Wiltfangah,ai,aj, Martin R. Turnerak, Inga Zerrai,al, Ron Handelsh,ab , Alexander G. Thompsonak , Gunilla Johanssonab, Natalia Ermanna, John Q. Trojanowskiac , Ilker Karacam, Holger Wagnerm, Patrick Oecklaf, Linda van Waalwijk van Doorne,f, Maria Bjerkek, Dimitrios Kapogiannisam, H. Bea Kuiperije,f, Lucia Farottip,YiLiw, Brian A. Gordonx,an , Stephane Epelbaumg, Stephanie J. B. Vosh, Catharina J. M. Klijne, William E. Van Nostrandao, Carolina Minguillonz, Matthias Schmitzai,al, Carla Galloap, Andrea Lopez Matoaq, Florence Thibautar , Simone Listas, Daniel Alcoleat,u , Henrik Zetterbergad,ae,as, Kaj Blennowad and Johannes Kornhubera , on Behalf of the Members of the WFSBP Task Force Working on this Topic: Peter Riederer, Carla Gallo, Dimitrios Kapogiannis, Andrea Lopez Mato, Florence Thibaut aDepartment of Psychiatry and Psychotherapy, Universit€atsklinikum Erlangen, and Friedrich-Alexander Universit€at Erlangen-Nurnberg,€ Erlangen, Germany; bDepartment of Neurodegeneration Diagnostics, Medical University of Białystok, and Department of Biochemical Diagnostics, University Hospital of Białystok, Białystok, Poland; cCenter of Mental Health, Clinic and Policlinic of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Wurzburg,€ Wurzburg,€ Germany; dInstitute for Healthy Aging, University of North Texas Health Science Center, Fort Worth, TX, USA; eDepartment of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Center, Nijmegen, The Netherlands; fDepartment of Laboratory Medicine, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer center, Nijmegen, The Netherlands; gInstitut de la M emoire et de la Maladie d’Alzheimer (IM2A), Salp^etri erie Hospital, INSERM UMR-S 975 (ICM), Paris 6 University, Paris, France; hDepartment of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands; iDepartment of Neurology, Alzheimer Centre, Amsterdam Neuroscience VU University Medical Centre, Amsterdam, The Netherlands; jInstitute of Clinical Neurobiology, Vienna, Austria; kReference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium; lDepartment of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium; mDepartment of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany; nInstitute of Human Genetics, University of Bonn, Bonn, Germany; oDepartment of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany; pSection of Neurology, Center for Memory Disturbances, Lab of Clinical Neurochemistry, University of Perugia, Perugia, Italy; qDepartment of Radiology, Mayo Clinic, Rochester, MN, USA; rNeurochemistry Lab and Biobank, Department of Clinical Chemistry, Amsterdam Neuroscience, VU University Medical Center Amsterdam, Amsterdam, The Netherlands; sAXA Research Fund & UPMC Chair, Sorbonne Universit es, Universit e Pierre et Marie Curie (UPMC) Paris 06, Inserm, CNRS, Institut du Cerveau et de la Moelle Epini ere (ICM), D epartement de Neurologie, Institut de la M emoire et de la Maladie d’Alzheimer (IM2A), Hopital^ Piti e-Salp^etri ere, Boulevard de l’hopital,^ Paris, France; tDepartment of Neurology, Institut d’Investigacions Biom ediques Sant Pau - Hospital de Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain; uCentro de Investigacion Biom edica en Red en Enfermedades Neurodegenerativas, CIBERNED, Spain; vGerman Center for Neurodegenerative Disorders (DZNE), Bonn, Germany; wCenter for Brain Health, Department of Psychiatry, NYU Langone Medical Center, New York, NY, USA; xKnight Alzheimer’s Disease Research Center, Washington University School of Medicine, Saint Louis, MO, USA; yDepartment of Neurology, Washington University School of Medicine, Saint Louis, MO, USA; zBarcelonabeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain; aaAlzheimer’s Disease and Other Cognitive Disorders Unit, Hospital Cl ınic, Institut d’Investigacions Biom ediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; abKarolinska Institutet, Department NVS, Center for Alzheimer Research, Division of Neurogeriatrics, Huddinge, Sweden; acDepartment of Pathology and Laboratory Medicine, Downloaded by [the Medical University of Vienna], [Professor Siegfried Kasper] at 06:38 03 November 2017 Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; adClinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Molndal,€ Sweden; aeInstitute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Molndal,€ Sweden; afDepartment of Neurology, University of Ulm, Ulm, Germany; agParacelsus-Elena-Klinik, Kassel and University Medical Center Gottingen,€ Department of Neurology, Gottingen,€ Germany; ahDepartment of Psychiatry & Psychotherapy, University of Gottingen,€ Gottingen,€ Germany; aiGerman Center for Neurodegenerative Diseases (DZNE), Gottingen,€ Germany; ajiBiMED, Medical Sciences Department, University of Aveiro, Aveiro, Portugal; akNuffield
CONTACT Piotr Lewczuk [email protected] Lab for Clinical Neurochemistry and Neurochemical Dementia Diagnostics, Department of Psychiatry and Psychotherapy, Schwabachanlage 6, 91054 Erlangen, Germany ß 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/Licenses/by- nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. 2 P. LEWCZUK ET AL.
Department of Clinical Neurosciences, University of Oxford, Oxford, UK; alClinical Dementia Centre, Department of Neurology, University Medical School, Gottingen,€ Germany; amLaboratory of Neurosciences, National Institute on Aging/National Institutes of Health (NIA/NIH), Baltimore, MD, USA; anDepartment of Radiology, Washington University School of Medicine, Saint Louis, MO, USA; aoDepartment of Neurosurgery, HSC T-12/086, Stony Brook University, New York, NY, USA; apDepartamento de Ciencias Celulares y Moleculares/Laboratorios de Investigaci on y Desarrollo, Facultad de Ciencias y Filosof ıa, Universidad Peruana Cayetano Heredia, Lima, Peru; aqChair of Psychoneuroimmunoendocrinology, Maimonides University, Buenos Aires, Argentina; arDepartment of Psychiatry, University Hospital Cochin-Site Tarnier 89 rue d’Assas, INSERM 894, Faculty of Medicine Paris Descartes, Paris, France; asDepartment of Molecular Neuroscience, UCL Institute of Neurology, London, UK
ABSTRACT ARTICLE HISTORY In the 12 years since the publication of the first Consensus Paper of the WFSBP on biomarkers Received 3 August 2017 of neurodegenerative dementias, enormous advancement has taken place in the field, and the Accepted 21 August 2017 Task Force takes now the opportunity to extend and update the original paper. New concepts KEYWORDS of Alzheimer’s disease (AD) and the conceptual interactions between AD and dementia due to Alzheimer’s disease; AD were developed, resulting in two sets for diagnostic/research criteria. Procedures for pre-ana- dementia; biomarkers; lytical sample handling, biobanking, analyses and post-analytical interpretation of the results cerebrospinal fluid; were intensively studied and optimised. A global quality control project was introduced to evalu- consensus ate and monitor the inter-centre variability in measurements with the goal of harmonisation of results. Contexts of use and how to approach candidate biomarkers in biological specimens other than cerebrospinal fluid (CSF), e.g. blood, were precisely defined. Important development was achieved in neuroimaging techniques, including studies comparing amyloid-b positron emis- sion tomography results to fluid-based modalities. Similarly, development in research laboratory technologies, such as ultra-sensitive methods, raises our hopes to further improve analytical and diagnostic accuracy of classic and novel candidate biomarkers. Synergistically, advancement in clinical trials of anti-dementia therapies energises and motivates the efforts to find and optimise the most reliable early diagnostic modalities. Finally, the first studies were published addressing the potential of cost-effectiveness of the biomarkers-based diagnosis of neurodegenerative disorders.
Introduction trait markers as invariable characteristics of a disease The concept of biomarkers in neurodegenerative e.g. gene mutations, and (g) state markers to follow disorders disease progression, e.g. enzymes, ions, etc. The most rigorous but most solid definitions of ‘a Twelve years after publication of the first WFSBP con- diagnostic biomarkers’ in the field of neurodegenera- sensus paper on the biomarkers of dementia disorders tive dementias, especially for Alzheimer’s disease (AD) (Wiltfang et al. 2005), the WFSBF Task Force now takes were those given by two National Institute on Aging the opportunity to update this consensus to reflect (NIA) and Alzheimer Association consensus conferences the most current state-of-the-art in the field. (Consensus Report of the Working Group 1998, Frank Pharmacological treatment strategies for neuropsychi- et al. 2003), as well as Shaw et al. (2007) and Gerlach et al. ‘ atric diseases have been developed in the times of neuro- (2012), which includes the following features: chemistry’ and since that time no real new therapeutic targets have been discovered for dementia disorders, linked to fundamental features of the Parkinson’s disease (PD), depression or schizophrenia, all neuropathology, of them characterised by high societal and personal bur- validated in neuropathologically confirmed cases, den. However, recent developments have led to define able to detect the disease early in its course and and test specific and selective biomarkers for the early distinguish it from other dementias, detection of neurodegenerative diseases.
Downloaded by [the Medical University of Vienna], [Professor Siegfried Kasper] at 06:38 03 November 2017 non-invasive, simple to use and inexpensive, The ‘biomarker concept’ includes a variety of pos- not influenced by symptomatic drug treatment. sible research strategies: (a) predictive biomarkers for estimating disease probability at the pre-clinical stage, The following criteria should be fulfilled before (b) diagnostic biomarkers, e.g. for precise differential acceptance as a valid biomarker for AD (Consensus diagnosis, (c) prognostic biomarkers for prognosis/ report of the Working Group 1998; Frank et al. 2003; chance of healing, (d) treatment response biomarkers Gerlach et al. 2012; Shaw et al. 2007): (‘theramarkers’) for estimating the response to therapy, (e) surrogate biomarkers for getting evidence, how sensitivity (>85%; 100% indicates that all patients intervention influences the endpoint of interest, (f) are identified with the disease), THE WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY 3