How to handle adsorption of cerebrospinal fluid amyloid β (1-42) in laboratory practice? Identifying problematic handlings and resolving the issue by use of the Aβ42/Aβ40 ratio

Alzheimers Dement. 2017 Aug;13(8):885-892. doi: 10.1016/j.jalz.2017.01.010. Epub 2017 Feb 21.

Abstract

Introduction: We aimed to investigate factors defining amyloid β (1-42) (Aβ1-42) adsorption during preanalytical workup of cerebrospinal fluid (CSF).

Methods: CSF was transferred to new tubes ≤4 times. Variables tested were different polypropylene tube brands, volumes, CSF Aβ1-42 concentrations, incubation times, pipettes, vortex intensities, and other CSF proteins, including hyperphosphorylated tau and Interleukin 1 Receptor Accessory Protein (IL-1RAcP). An enquiry assessed the number of transfers in current practice.

Results: In diagnostic practice, the number of transfers varied between 1 and 3. Every tube transfer resulted in 5% loss of Aβ1-42 concentration, even 10% in small volumes. Adsorption was observed after 30 seconds and after contact with the pipette tip. Tube brand, vortexing, or continuous tube movement did not influence adsorption. Adsorption for Aβ1-40 was similar, resulting in stable Aβ1-42/Aβ1-40 ratios over multiple tube transfers.

Discussion: We confirmed that adsorption of CSF Aβ1-42 during preanalytical processing is an important confounder. However, use of the Aβ1-42/Aβ1-40 ratio overcomes this effect and can therefore contribute to increased diagnostic accuracy.

Keywords: Adsorption; Alzheimer's disease; Amyloid β (1–40); Amyloid β (1–42); Biobanking; Biomarkers; Cerebrospinal fluid; Preanalytical variation; Ratio Aβ(42)/Aβ(40).

MeSH terms

  • Adsorption
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Amyloid beta-Peptides / chemistry
  • Biomarkers / cerebrospinal fluid
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Linear Models
  • Peptide Fragments / cerebrospinal fluid*
  • Peptide Fragments / chemistry
  • Pre-Analytical Phase / instrumentation
  • Surveys and Questionnaires
  • Time Factors

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)