The impact of preanalytical variables on measuring cerebrospinal fluid biomarkers for Alzheimer's disease diagnosis: A review

Oskar Hansson, Alvydas Mikulskis, Anne M. Fagan, Charlotte Teunissen, Henrik Zetterberg, Hugo Vanderstichele, Jose Luis Molinuevo, Leslie M. Shaw, Manu Vandijck, Marcel M. Verbeek, Mary Savage, Niklas Mattsson, Piotr Lewczuk, Richard Batrla, Sandra Rutz, Robert A. Dean, Kaj Blennow

Research output: Contribution to journalReview article

24 Scopus citations

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.

Original languageEnglish
Pages (from-to)1313-1333
Number of pages21
JournalAlzheimer's and Dementia
Volume14
Issue number10
DOIs
StatePublished - Oct 2018

Keywords

  • Alzheimer's disease diagnosis
  • Biomarkers
  • Cerebrospinal fluid
  • Phosphorylated tau
  • Preanalytical variables
  • Total tau
  • β-Amyloid 42

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    Hansson, O., Mikulskis, A., Fagan, A. M., Teunissen, C., Zetterberg, H., Vanderstichele, H., Molinuevo, J. L., Shaw, L. M., Vandijck, M., Verbeek, M. M., Savage, M., Mattsson, N., Lewczuk, P., Batrla, R., Rutz, S., Dean, R. A., & Blennow, K. (2018). The impact of preanalytical variables on measuring cerebrospinal fluid biomarkers for Alzheimer's disease diagnosis: A review. Alzheimer's and Dementia, 14(10), 1313-1333. https://doi.org/10.1016/j.jalz.2018.05.008