Review

. 2018 Mar 15;10(1):30.

doi: 10.1186/s13195-018-0359-x.

White paper by the Society for CSF Analysis and Clinical Neurochemistry: Overcoming barriers in biomarker development and clinical translation

Charlotte E Teunissen¹, Markus Otto², Sebastiaan Engelborghs^{3

4}, Sanna-Kaisa Herukka⁵, Sylvain Lehmann⁶, Piotr Lewczuk^{7

8

9

10}, Alberto Lleó^{11

12}, Armand Perret-Liaudet^{13

14}, Hayrettin Tumani^{15

16}, Martin R Turner¹⁷, Marcel M Verbeek¹⁸, Jens Wiltfang^{19

20

21}, Henrik Zetterberg^{22

23

24

25}, Lucilla Parnetti²⁶, Kaj Blennow^{22

23}

Affiliations

¹ Neurochemistry Lab and Biobank, Department of Clinical Chemistry, Amsterdam Neuroscience, VU University Medical Center Amsterdam, Amsterdam, The Netherlands. c.teunissen@vumc.nl.
² Department of Neurology, University of Ulm, Ulm, Germany.
³ Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium.
⁴ Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium.
⁵ Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
⁶ Université de Montpellier, University Hospital, INSERM U1183, Montpellier, France.
⁷ Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, Erlangen, Germany.
⁸ Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
⁹ Department of Neurodegeneration Diagnostics, Medical University of Białystok, Białystok, Poland.
¹⁰ Department of Biochemical Diagnostics, University Hospital of Białystok, Białystok, Poland.
¹¹ Memory Unit, Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau, Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
¹² Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain.
¹³ Neurobiology Laboratory, Department of Biochemistry and Molecular Biology, Hospices Civils de Lyon, Lyon, France.
¹⁴ University of Lyon 1, CNRS UMR5292, INSERM U1028, BioRan, Lyon, France.
¹⁵ Department of Neurology, CSF Laboratory, MS Outpatient Unit, University Hospital of Ulm, Ulm, Germany.
¹⁶ Specialty Hospital of Neurology Dietenbronn, Acadamic Hospital of University of Ulm, Schwendi, Germany.
¹⁷ Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
¹⁸ Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Departments of Neurology and Laboratory Medicine, Radboud Alzheimer Centre, Nijmegen, The Netherlands.
¹⁹ Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August University, Goettingen, Germany.
²⁰ German Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany.
²¹ iBiMED, Medical Sciences Department, University of Aveiro, Aveiro, Portugal.
²² Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
²³ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
²⁴ Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
²⁵ UK Dementia Research Institute at UCL, London, UK.
²⁶ Center for Memory Disturbances, Lab of Clinical Neurochemistry, Section of Neurology, Department of Medicine, University of Perugia, Perugia, Italy.

PMID: 29544527
PMCID: PMC5855933
DOI: 10.1186/s13195-018-0359-x

Review

White paper by the Society for CSF Analysis and Clinical Neurochemistry: Overcoming barriers in biomarker development and clinical translation

Charlotte E Teunissen et al. Alzheimers Res Ther. 2018.

. 2018 Mar 15;10(1):30.

doi: 10.1186/s13195-018-0359-x.

Authors

Affiliations

¹ Neurochemistry Lab and Biobank, Department of Clinical Chemistry, Amsterdam Neuroscience, VU University Medical Center Amsterdam, Amsterdam, The Netherlands. c.teunissen@vumc.nl.
² Department of Neurology, University of Ulm, Ulm, Germany.
³ Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium.
⁴ Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium.
⁵ Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
⁶ Université de Montpellier, University Hospital, INSERM U1183, Montpellier, France.
⁷ Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, Erlangen, Germany.
⁸ Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
⁹ Department of Neurodegeneration Diagnostics, Medical University of Białystok, Białystok, Poland.
¹⁰ Department of Biochemical Diagnostics, University Hospital of Białystok, Białystok, Poland.
¹¹ Memory Unit, Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau, Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
¹² Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain.
¹³ Neurobiology Laboratory, Department of Biochemistry and Molecular Biology, Hospices Civils de Lyon, Lyon, France.
¹⁴ University of Lyon 1, CNRS UMR5292, INSERM U1028, BioRan, Lyon, France.
¹⁵ Department of Neurology, CSF Laboratory, MS Outpatient Unit, University Hospital of Ulm, Ulm, Germany.
¹⁶ Specialty Hospital of Neurology Dietenbronn, Acadamic Hospital of University of Ulm, Schwendi, Germany.
¹⁷ Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
¹⁸ Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Departments of Neurology and Laboratory Medicine, Radboud Alzheimer Centre, Nijmegen, The Netherlands.
¹⁹ Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August University, Goettingen, Germany.
²⁰ German Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany.
²¹ iBiMED, Medical Sciences Department, University of Aveiro, Aveiro, Portugal.
²² Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
²³ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
²⁴ Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
²⁵ UK Dementia Research Institute at UCL, London, UK.
²⁶ Center for Memory Disturbances, Lab of Clinical Neurochemistry, Section of Neurology, Department of Medicine, University of Perugia, Perugia, Italy.

PMID: 29544527
PMCID: PMC5855933
DOI: 10.1186/s13195-018-0359-x

Abstract

Body fluid biomarkers have great potential for different clinical purposes, including diagnosis, prognosis, patient stratification and treatment effect monitoring. This is exemplified by current use of several excellent biomarkers, such as the Alzheimer's disease cerebrospinal fluid (CSF) biomarkers, anti-neuromyelitis optica antibodies and blood neurofilament light. We still, however, have a strong need for additional biomarkers and several gaps in their development and implementation should be filled. Examples of such gaps are i) limited knowledge of the causes of neurological diseases, and thus hypotheses about the best biomarkers to detect subclinical stages of these diseases; ii) the limited success translating discoveries obtained by e.g. initial mass spectrometry proteomic low-throughput studies into immunoassays for widespread clinical implementation; iii) lack of interaction among all stakeholders to optimise and adapt study designs throughout the biomarker development process to medical needs, which may change during the long period needed for biomarker development.The Society for CSF Analysis and Clinical Neurochemistry (established in 2015) has been founded as a concerted follow-up of large standardisation projects, including BIOMARKAPD and SOPHIA, and the BioMS-consortium.The main aims of the CSF society are to exchange high level international scientific experience, to facilitate the incorporation of CSF diagnostics into clinical practice and to give advice on inclusion of CSF analysis into clinical guidelines. The society has a broad scope, as its vision is that the gaps in development and implementation of biomarkers are shared among almost all neurological diseases and thus they can benefit from the activities of the society.

Keywords: Assay development; Biomarker discovery; Body fluids; Cerebrospinal fluid; Clinical implementation; Education Biomarkers; Neurology; Society.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

Dr Teunissen has functioned in advisory boards of Fujirebio and Roche, received non-financial support in the form of research consumables from ADxNeurosciences and Euroimmun, performed contract research or received grants from Janssen prevention center, Boehringer, Brainsonline, AxonNeurosciences, EIP farma, Probiodrug and Roche which are all unrelated to the present work.

Dr Otto gave invited talks for Teva, Virion, Fujirebio and Lilly and gave scientific advice to Axon, Biogen, Ionis, Roche and Neuroalliance.

Dr Engelborghs has received unrestricted research grants from Janssen Pharmaceutica NV and ADx Neurosciences (paid to institution).

Dr Herukka has no conflicts to report.

Dr Lehmann received consultation honoraria from Fujirebio Europe.

Dr Lewczuk received consultation and lectures honoraria from Innogenetics/Fujirebio Europe, IBL International, AJ Roboscreen, and Roche.

Dr Lleó MD, PhD has received speaker honoraria from Novartis, Esteva, Nutricia and Lilly and fees for advisory board meetings for Nutricia, Novartis, Schwabe and Lilly.

Dr Perret-Liaudet received funding for travel from Innogenetics/Fujirebio, Roche, Siemens and AJ Robosceen (in the context of lectures).

Dr Tumani received funding for research projects, lectures and travel from Bayer, Biogen, Genzyme, Fresenius, Merck, Novartis, Roche, Siemens Health Diagnostic and Teva.

Dr Wiltfang received personal fees (advisory boards or consulting) from Axon Neuroscience, Eli Lilly, Janssen-Cilag GmbH, MSD Sharp & Dohme GmbH, F. Hoffmann-La Roche.

Henrik Zetterberg MD, PhD is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg. He has served on advisory boards of Roche Diagnostics, Eli Lilly and Pharmasum Therapeutics and has received a travel grant from TEVA.

L. Parnetti MD, PhD has received honoraria as a member of advisory boards from Innogenetics/Fujirebio Europe, IBL International and Roche.

Dr Blennow has served as a consultant or on advisory boards for Alzheon, BioArctic, Biogen, Eli Lilly, Fujirebio Europe, IBL International, Merck, Pfizer and Roche Diagnostics and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Venture-based platform company at the University of Gothenburg.

Dr Herukka, Dr Turner MD and Dr Verbeek have no conflicts to report.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

**Fig. 1**
Steps in the biomarker development process

See this image and copyright information in PMC

References

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White paper by the Society for CSF Analysis and Clinical Neurochemistry: Overcoming barriers in biomarker development and clinical translation

Affiliations

White paper by the Society for CSF Analysis and Clinical Neurochemistry: Overcoming barriers in biomarker development and clinical translation

Authors

Affiliations

Abstract

Conflict of interest statement

Ethics approval and consent to participate

Consent for publication

Competing interests

Publisher’s Note

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical