Effect of Tween-20 on Core Biomarkers Measured in Cerebrospinal Fluid from Patients with Alzheimer's Disease, Mild Cognitive Impairment, or Healthy Control Individuals

J Alzheimers Dis. 2016;49(2):493-502. doi: 10.3233/JAD-150234.

Abstract

Background: There is substantial variation caused by preanalytical procedures in the measurement of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) reported in the literature.

Objective: Determine whether the detergent Tween-20 improves diagnostic accuracy.

Methods: CSF proteins (Aβ42, Aβ40, total tau, and phosphorylated tau) were measured by standard ELISA, in uncentrifuged CSF with or without 0.05% Tween-20 from patients with AD or amnestic mild cognitive impairment, and healthy elderly controls. In the main study, collection tubes containing Tween-20 (Sarstedt 15 mL) were filled with 5 mL CSF to ensure consistent detergent concentration across subsequent aliquots into Corning 2 mL tubes. These latter were also the primary collection vessel for samples without Tween-20. The effect of centrifugation, and extra tube transfer of samples with Tween-20 were also examined.

Results: 0.05% Tween-20 significantly increased mean measured CSF concentration of Aβ42 (30% ), Aβ40 (23% ), and total tau (4% ), but not phosphorylated tau. Generally, these increases were similar in all groups, although for Aβ42, the mean percentage increase with Tween-20 was slightly larger for AD. Areas under receiver-operator characteristic curves were similar whether Tween-20 was present or not. Centrifuged CSF without Tween-20 significantly reduced the measured concentration of Aβ42 versus non-centrifuged samples, a difference not seen when detergent was added. Similar CSF Aβ42 levels were found whether Tween-20 was added at collection in an extra tube or directly to the main collection tube.

Conclusion: Addition of Tween-20 to CSF did not improve differentiation of patients from controls.

Keywords: Amyloid beta-peptides; dementia; human; synthetic detergent; tau protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid*
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Amyloid beta-Peptides / drug effects*
  • Cognitive Dysfunction / cerebrospinal fluid*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Peptide Fragments / cerebrospinal fluid
  • Peptide Fragments / drug effects*
  • Phosphorylation / drug effects
  • Polysorbates / pharmacology*
  • ROC Curve
  • Surface-Active Agents / pharmacology*
  • tau Proteins / cerebrospinal fluid
  • tau Proteins / drug effects*

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • Polysorbates
  • Surface-Active Agents
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)
  • tau Proteins