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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

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Volume 51, Issue 12 (Dec 2013)


Identification of an important potential confound in CSF AD studies: aliquot volume

Jamie Toombs
  • Corresponding author
  • Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK
  • Jamie Toombs and Ross W. Paterson contributed equally to this work.
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Ross W. Paterson
  • Corresponding author
  • Department of Neurodegeneration, Institute of Neurology, Dementia Research Centre, London, UK
  • Jamie Toombs and Ross W. Paterson contributed equally to this work.
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Michael P. Lunn / Jenifer M. Nicholas / Nick C. Fox / Miles D. Chapman / Jonathan M. Schott / Henrik Zetterberg
  • Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK
  • Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2013-08-12 | DOI: https://doi.org/10.1515/cclm-2013-0293


Background: Cerebrospinal fluid (CSF) amyloid β1-42 (Aβ1-42), total tau (T-tau) and phosphorylated tau181 (P-tau) are finding increasing utility as biomarkers of Alzheimer’s disease (AD). The purpose of this study was to determine whether measured CSF biomarker concentrations were affected by aliquot storage volume and whether addition of detergent-containing buffer mitigates any observed effects.

Methods: AD and control CSF was distributed into polypropylene tubes in aliquots of different volumes (50–1500 μL). Aβ1-42, T-tau and P-tau were measured with and without addition of Tween 20 (0.05%).

Results: Measured concentrations of Aβ1-42 increased two-fold with aliquot storage volume. A volume increase of 10 µL caused an Aβ1-42 increase of 0.95 pg/mL [95% confidence interval (CI) 0.36–1.50, p=0.02] in controls, and 0.60 pg/mL (CI 0.23–0.98 pg/mL, p=0.003) in AD samples. Following addition of Tween 20, the positive relationship between Aβ1-42 and aliquot volume disappeared. T-tau and P-tau were not significantly affected.

Conclusions: CSF aliquot storage volume has a significant impact on the measured concentration of Aβ1-42. The introduction of a buffer detergent at the initial aliquoting stage may be an effective solution to this problem.

This article offers supplementary material which is provided at the end of the article.

Keywords: Alzheimer’s disease; amyloid β; cerebrospinal fluid; tau; volume


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About the article

Corresponding authors: Jamie Toombs, Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK, Phone: +44 20 34483553, E-mail: ; and Ross W. Paterson, Dementia Research Centre, Department of Neurodegeneration, Institute of Neurology, London, UK, Phone: +44 20 3448 3553, E-mail:

Received: 2013-04-17

Accepted: 2013-07-17

Published Online: 2013-08-12

Published in Print: 2013-12-01

Citation Information: Clinical Chemistry and Laboratory Medicine, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2013-0293.

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©2013 by Walter de Gruyter Berlin Boston. Copyright Clearance Center

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