Reference measurement procedures for Alzheimer’s disease cerebrospinal fluid biomarkers: definitions and approaches with focus on amyloid β42

Author:

Mattsson Niklas1,Zegers Ingrid2,Andreasson Ulf3,Bjerke Maria3,Blankenstein Marinus A4,Bowser Robert5,Carrillo Maria C6,Gobom Johan3,Heath Theresa7,Jenkins Rand8,Jeromin Andreas9,Kaplow June10,Kidd Daniel11,Laterza Omar F12,Lockhart Andrew13,Lunn Michael P14,Martone Robert L15,Mills Kevin16,Pannee Josef3,Ratcliffe Marianne17,Shaw Leslie M18,Simon Adam J19,Soares Holly20,Teunissen Charlotte E4,Verbeek Marcel M21,Umek Robert M22,Vanderstichele Hugo23,Zetterberg Henrik24,Blennow Kaj3,Portelius Erik3

Affiliation:

1. Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, SE-431 80 Mölndal, Sweden.

2. Institute for Reference Materials and Measurements (IRMM), Joint Research Centre, European Commission, Geel, Belgium

3. Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, SE-431 80 Mölndal, Sweden

4. Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands

5. Barrow Neurological Institute, Divisions of Neurology and Neurobiology, St. Joseph’s Hospital & Medical Center, Phoenix, AZ, USA

6. Alzheimers Association, Medical & Scientific Relations Division, Chicago, IL, USA

7. BARC Global Central Labs, a division of Cerba European Lab, New York, NY, USA

8. PPD Bioanalytical Laboratory, Richmond, VA, USA

9. Banyan Biomarkers, Inc., Alachua, FL, USA

10. Eisai Medical Research, Woodcliff Lake, NJ, USA

11. Janssen Alzheimer Immunotherapy Research & Development LLC, South San Francisco, CA, USA

12. Clinical Development Laboratory, Merck & Co., NJ, USA

13. Discovery Medicine, GlaxoSmithKline R&D China, Clinical Unit Cambridge, Addenbrooke’s Hospital, Cambridge, UK

14. Neuroimmunologyand CSF Laboratory, National Hospital for Neurology. UCL Institute of Neurology, London, UK

15. Biomarker Center of Excellence, Covance Inc., Greenfield, IN, USA

16. Clinical & Molecular Genetics Unit, Institute of Child Health & Great Ormond Street Hospital for Sick Children, University College London, London, UK

17. Personalised Healthcare & Biomarkers, AstraZeneca R&D, Macclesfield, UK

18. Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

19. AJ Simon Enterprises LLC, 1310 Prospect Farm Dr, Yardley, PA, USA

20. Translational Medicine, BioTherapeutics, Pfizer Inc., South San Francisco, CA, USA

21. Radboud University Nijmegen Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Departments of Neurology & Laboratory Medicine & Alzheimer Centre, Nijmegen, The Netherlands

22. Meso Scale Discovery, Gaithersburg, MD, USA

23. ADx Neurosciences, Gent, Belgium

24. Clinical Neurochemistry Laboratory, Institute of Neuroscience & Physiology, Department of Psychiatry & Neurochemistry, the Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden and UCL Institute of Neurology, Queen Square, London, UK

Abstract

Cerebrospinal fluid (CSF) biomarkers for Alzheimer’s disease (AD) are increasingly used in clinical settings, research and drug trials. However, their broad-scale use on different technology platforms is hampered by the lack of standardization at the level of sample handling, determination of concentrations of analytes and the absence of well-defined performance criteria for in vitro diagnostic or companion diagnostic assays, which influences the apparent concentration of the analytes measured and the subsequent interpretation of the data. There is a need for harmonization of CSF AD biomarker assays that can reliably, across centers, quantitate CSF biomarkers with high analytical precision, selectivity and stability over long time periods. In this position paper, we discuss reference procedures for the measurement of CSF AD biomarkers, especially amyloid β42 and tau. We describe possible technical approaches, focusing on a selected reaction monitoring mass spectrometry assay as a candidate reference method for quantification of CSF amyloid β42.

Publisher

Future Medicine Ltd

Subject

Biochemistry (medical),Clinical Biochemistry,Drug Discovery

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