Oskar Hansson1, Alvydas Mikulskis2, Anne M Fagan3, Charlotte Teunissen4, Henrik Zetterberg5, Hugo Vanderstichele6, Jose Luis Molinuevo7, Leslie M Shaw8, Manu Vandijck9, Marcel M Verbeek10, Mary Savage11, Niklas Mattsson12, Piotr Lewczuk13, Richard Batrla14, Sandra Rutz15, Robert A Dean16, Kaj Blennow17. 1. Department of Neurology, Skåne University Hospital, Lund, Sweden; Memory Clinic, Skåne University Hospital, Malmö, Sweden. Electronic address: oskar.hansson@med.lu.se. 2. Biogen, Boston, MA, USA. 3. Department of Neurology, Washington University School of Medicine, St Louis, MO, USA. 4. VU University Medical Center, Amsterdam, The Netherlands. 5. UK Dementia Research Institute, London, UK; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. 6. ADx NeuroSciences, Gent, Belgium. 7. BarcelonaBeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain. 8. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 9. Fujirebio-Europe NV, Gent, Belgium. 10. Radboud University Medical Center, Departments of Neurology and Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands. 11. Merck and Company, West Point, PA, USA. 12. Department of Neurology, Skåne University Hospital, Lund, Sweden. 13. Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, and Friedrich-Alexander Universität Erlangen-Nürnberg, Germany; Department of Neurodegeneration Diagnostics, Medical University of Bialystok, Poland. 14. Roche Diagnostics GmbH, Rotkreuz, Switzerland. 15. Roche Diagnostics GmbH, Penzberg, Germany. 16. Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. 17. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Abstract
INTRODUCTION: Cerebrospinal fluid (CSF) biomarkers have the potential to improve the diagnostic accuracy of Alzheimer's disease, yet there is a lack of harmonized preanalytical CSF handling protocols. METHODS: This systematic review summarizes the current literature on the influence of preanalytical variables on CSF biomarker concentration. We evaluated the evidence for three core CSF biomarkers: β-amyloid 42, total tau, and phosphorylated tau. RESULTS: The clinically important variables with the largest amount of conflicting data included the temperature at which samples are stored, the time nonfrozen samples can be stored, and possible effects of additives such as detergents, blood contamination, and centrifugation. Conversely, we discovered that there is consensus that tube material has a significant effect. DISCUSSION: A unified CSF handling protocol is recommended to reduce preanalytical variability and facilitate comparison of CSF biomarkers across studies and laboratories. In future, experiments should use a gold standard with fresh CSF collected in low binding tubes.
INTRODUCTION: Cerebrospinal fluid (CSF) biomarkers have the potential to improve the diagnostic accuracy of Alzheimer's disease, yet there is a lack of harmonized preanalytical CSF handling protocols. METHODS: This systematic review summarizes the current literature on the influence of preanalytical variables on CSF biomarker concentration. We evaluated the evidence for three core CSF biomarkers: β-amyloid 42, total tau, and phosphorylated tau. RESULTS: The clinically important variables with the largest amount of conflicting data included the temperature at which samples are stored, the time nonfrozen samples can be stored, and possible effects of additives such as detergents, blood contamination, and centrifugation. Conversely, we discovered that there is consensus that tube material has a significant effect. DISCUSSION: A unified CSF handling protocol is recommended to reduce preanalytical variability and facilitate comparison of CSF biomarkers across studies and laboratories. In future, experiments should use a gold standard with fresh CSF collected in low binding tubes.
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