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CSF biomarkers for dementia
  1. Ashvini Keshavan1,
  2. Frankie O’Shea1,
  3. Miles D Chapman2,3,
  4. Melanie S Hart2,3,
  5. Michael PT Lunn2,4,
  6. Ross W Paterson1,
  7. Jonathan D Rohrer5,
  8. Catherine J Mummery6,
  9. Nick C Fox1,
  10. Henrik Zetterberg7,8,
  11. Jonathan M Schott1
  1. 1 Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK
  2. 2 Neuroimmunology and CSF Laboratory, National Hospital for Neurology and Neurosurgery, London, UK
  3. 3 Department of Neuroinflammation, UCL Queen Square Institute of Neurology, London, UK
  4. 4 MRC Centre for Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK
  5. 5 Dementia Research Centre, Department of Neurodegenerative Disease, University College London Institute of Neurology, London, UK
  6. 6 Dementia Research Centre, Department of Neurodegenerative Disease, National Hospital for Neurology and Neurosurgery, London, UK
  7. 7 Fluid Biomarkers Laboratory, UK DRI at University College London, UK Dementia Research Institute, London, UK
  8. 8 Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg Sahlgrenska Academy, Goteborg, Sweden
  1. Correspondence to Professor Jonathan M Schott, Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK; j.schott{at}ucl.ac.uk

Abstract

Although cerebrospinal fluid (CSF) biomarker testing is incorporated into some current guidelines for the diagnosis of dementia (such as England's National Institute for Health and Care Excellence (NICE)), it is not widely accessible for most patients for whom biomarkers could potentially change management. Here we share our experience of running a clinical cognitive CSF service and discuss recent developments in laboratory testing including the use of the CSF amyloid-β 42/40 ratio and automated assay platforms. We highlight the importance of collaborative working between clinicians and laboratory staff, of preanalytical sample handling, and discuss the various factors influencing interpretation of the results in appropriate clinical contexts. We advocate for broadening access to CSF biomarkers by sharing clinical expertise, protocols and interpretation with colleagues working in psychiatry and elderly care, especially when access to CSF may be part of a pathway to disease-modifying treatments for Alzheimer’s disease and other forms of dementia.

  • CSF
  • alzheimer disease
  • amyloid
  • dementia
  • health policy & practice

https://doi.org/10.1136/practneurol-2021-003310

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    Footnotes

    • Twitter @AshviniKeshavan, @mike_the_nerve, @ftdtalk, @jmschott

    • Contributors AK and JMS conceived of and drafted the main manuscript. All authors contributed significantly to the content of the manuscript and reviewed the drafts and provided feedback.

    • Funding AK is supported by a Weston Brain Institute and Selfridges Group Foundation award (UB170045). RWP is supported by an Alzheimer’s Association Clinician Scientist Fellowship and the UK Dementia Research Institute. JDR is supported by the Miriam Marks Brain Research UK Senior Fellowship and has received funding from an MRC Clinician Scientist Fellowship (MR/M008525/1) and the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), the AD Strategic Fund and the Alzheimer's Association (#ADSF-21-831376-C, #ADSF-21-831381-C and #ADSF-21-831377-C), the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2019-0228), the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE) and the European Union Joint Program for Neurodegenerative Disorders (JPND2021-00694). JMS is supported by Engineering and Physical Sciences Research Council (EP/J020990/1), British Heart Foundation (PG/17/90/33415) and EU’s Horizon 2020 research and innovation programme (666992). NCF and HZ are supported by UK Dementia Research Institute at University College London. MSH, MPTL, RWP, JDR, CJM, NCF and JMS are supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre.

    • Competing interests RWP is codirector of the NfL consortium (an industry-funded research consortium) and has given educational lectures sponsored by GE Healthcare. JDR has served on a medical advisory board and had a consultancy agreement with Alector, Arkuda Therapeutics, Wave Life Sciences and Prevail Therapeutics, and had a consultancy agreement also with UCB, AC Immune, Astex Pharmaceuticals, Biogen, Takeda and Eisai. CJM has been an advisor to IONIS, Biogen, Lilly and Roche, is on the international steering committee for aducanumab, and has lectured for Biogen. NCF’s research group has received payment for consultancy or for conducting studies from Biogen, Eli Lilly Research Laboratories, Ionis and Roche. NCF received no personal compensation for the aforementioned activities. NCF also serves on a Data Safety Monitoring Board for Biogen. JMS has received research funding from Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly), has consulted for Roche Pharmaceuticals, Biogen, Merck, and Eli Lilly, given educational lectures sponsored by GE Healthcare, Eli Lilly, and Biogen, and serves on a data safety monitoring committee for Axon Neuroscience SE. HZ has served at scientific advisory boards and/or as a consultant for Abbvie, Alector, Annexon, Artery Therapeutics, AZTherapies, CogRx, Denali, Eisai, Nervgen, Pinteon Therapeutics, Red Abbey Labs, Passage Bio, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave; and has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, Biogen and Roche. HZ is a cofounder of Brain Biomarker Solutions in Gothenburg AB, which is a part of the GU Ventures Incubator Programme.

    • Provenance and peer review Commissioned; externally reviewed by Emma Devenney, Sydney, Australia.

    Linked Articles

    • Editors’ commentary
      Highlights from this issue
      Phil E M Smith Geraint N Fuller
      Practical Neurology 2022; 22 261-261 Published Online First: 18 Jul 2022. doi: 10.1136/practneurol-2022-003520

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