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

Hansson, Oskar LU ; Mikulskis, Alvydas; Fagan, Anne M.; Teunissen, Charlotte; Zetterberg, Henrik LU ; Vanderstichele, Hugo; Molinuevo, Jose Luis; Shaw, Leslie M.; Vandijck, Manu and Verbeek, Marcel M., et al. (2018) In Alzheimer's and Dementia 14(10). p.1313-1333
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... (More)

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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Please use this url to cite or link to this publication:
@article{e34b682d-f621-46a7-8948-f65fd44a3858,
  abstract     = {<p>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.</p>},
  author       = {Hansson, Oskar and Mikulskis, Alvydas and Fagan, Anne M. and Teunissen, Charlotte and Zetterberg, Henrik and Vanderstichele, Hugo and Molinuevo, Jose Luis and Shaw, Leslie M. and Vandijck, Manu and Verbeek, Marcel M. and Savage, Mary and Mattsson, Niklas and Lewczuk, Piotr and Batrla, Richard and Rutz, Sandra and Dean, Robert A. and Blennow, Kaj},
  issn         = {1552-5260},
  keyword      = {Alzheimer's disease diagnosis,Biomarkers,Cerebrospinal fluid,Phosphorylated tau,Preanalytical variables,Total tau,β-Amyloid 42},
  language     = {eng},
  number       = {10},
  pages        = {1313--1333},
  publisher    = {Elsevier},
  series       = {Alzheimer's and Dementia},
  title        = {The impact of preanalytical variables on measuring cerebrospinal fluid biomarkers for Alzheimer's disease diagnosis : A review},
  url          = {http://dx.doi.org/10.1016/j.jalz.2018.05.008},
  volume       = {14},
  year         = {2018},
}