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 articleAcademicpeer-review

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
JournalAlzheimer's and Dementia
Volume14
Issue number10
DOIs
Publication statusPublished - 2018

Cite this

Hansson, Oskar ; Mikulskis, Alvydas ; Fagan, Anne M. ; Teunissen, Charlotte ; Zetterberg, Henrik ; Vanderstichele, Hugo ; Molinuevo, Jose Luis ; Shaw, Leslie M. ; Vandijck, Manu ; Verbeek, Marcel M. ; Savage, Mary ; Mattsson, Niklas ; Lewczuk, Piotr ; Batrla, Richard ; Rutz, Sandra ; Dean, Robert A. ; Blennow, Kaj. / The impact of preanalytical variables on measuring cerebrospinal fluid biomarkers for Alzheimer's disease diagnosis: A review. In: Alzheimer's and Dementia. 2018 ; Vol. 14, No. 10. pp. 1313-1333.
@article{508b832997394ddcabe35d6808dbb363,
title = "The impact of preanalytical variables on measuring cerebrospinal fluid biomarkers for Alzheimer's disease diagnosis: A review",
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.",
author = "Oskar Hansson and Alvydas Mikulskis and Fagan, {Anne M.} and Charlotte Teunissen and Henrik Zetterberg and Hugo Vanderstichele and Molinuevo, {Jose Luis} and Shaw, {Leslie M.} and Manu Vandijck and Verbeek, {Marcel M.} and Mary Savage and Niklas Mattsson and Piotr Lewczuk and Richard Batrla and Sandra Rutz and Dean, {Robert A.} and Kaj Blennow",
year = "2018",
doi = "10.1016/j.jalz.2018.05.008",
language = "English",
volume = "14",
pages = "1313--1333",
journal = "Alzheimers & Dementia",
issn = "1552-5260",
publisher = "Elsevier",
number = "10",

}

Hansson, O, Mikulskis, A, Fagan, AM, Teunissen, C, Zetterberg, H, Vanderstichele, H, Molinuevo, JL, Shaw, LM, Vandijck, M, Verbeek, MM, Savage, M, Mattsson, N, Lewczuk, P, Batrla, R, Rutz, S, Dean, RA & Blennow, K 2018, 'The impact of preanalytical variables on measuring cerebrospinal fluid biomarkers for Alzheimer's disease diagnosis: A review' Alzheimer's and Dementia, vol. 14, no. 10, pp. 1313-1333. https://doi.org/10.1016/j.jalz.2018.05.008

The impact of preanalytical variables on measuring cerebrospinal fluid biomarkers for Alzheimer's disease diagnosis: A review. / Hansson, Oskar; Mikulskis, Alvydas; Fagan, Anne M.; Teunissen, Charlotte; Zetterberg, Henrik; Vanderstichele, Hugo; Molinuevo, Jose Luis; Shaw, Leslie M.; Vandijck, Manu; Verbeek, Marcel M.; Savage, Mary; Mattsson, Niklas; Lewczuk, Piotr; Batrla, Richard; Rutz, Sandra; Dean, Robert A.; Blennow, Kaj.

In: Alzheimer's and Dementia, Vol. 14, No. 10, 2018, p. 1313-1333.

Research output: Contribution to journalReview articleAcademicpeer-review

TY - JOUR

T1 - The impact of preanalytical variables on measuring cerebrospinal fluid biomarkers for Alzheimer's disease diagnosis: A review

AU - Hansson, Oskar

AU - Mikulskis, Alvydas

AU - Fagan, Anne M.

AU - Teunissen, Charlotte

AU - Zetterberg, Henrik

AU - Vanderstichele, Hugo

AU - Molinuevo, Jose Luis

AU - Shaw, Leslie M.

AU - Vandijck, Manu

AU - Verbeek, Marcel M.

AU - Savage, Mary

AU - Mattsson, Niklas

AU - Lewczuk, Piotr

AU - Batrla, Richard

AU - Rutz, Sandra

AU - Dean, Robert A.

AU - Blennow, Kaj

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85054153726&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/29940161

U2 - 10.1016/j.jalz.2018.05.008

DO - 10.1016/j.jalz.2018.05.008

M3 - Review article

VL - 14

SP - 1313

EP - 1333

JO - Alzheimers & Dementia

JF - Alzheimers & Dementia

SN - 1552-5260

IS - 10

ER -