title: 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/Aβ40ratio.
abstract: BACKGROUND
  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 Aβ1-42concentrations, 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 Aβ1-42concentration, 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 Aβ1-40was similar, resulting in stable Aβ1-42/Aβ1-40ratios over multiple tube transfers.
  
  
  CONCLUSIONS
  We confirmed that adsorption of CSF Aβ1-42during preanalytical processing is an important confounder. However, use of the Aβ1-42/Aβ1-40ratio overcomes this effect and can therefore contribute to increased diagnostic accuracy.
authors.affiliation: Neurochemistry Laboratory, Department of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands; Department of Neurology, Alzheimer Center, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: e.willemse@vumc.nl.
authors.forename: Eline
authors.initials: E
authors.lastname: Willemse
authors.affiliation: Neurochemistry Laboratory, Department of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Kees
authors.initials: K
authors.lastname: van Uffelen
authors.affiliation: Neurodegenerative Diseases Department, EUROIMMUN Medizinische Labordiagnostika AG, Lübeck, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Brix
authors.affiliation: Department of Biomedical Sciences, Reference Centre for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerpen, Belgium; Department of Neurology and Memory Clinic, Hospital Network Antwerp, Antwerpen, Belgium.
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Engelborghs
authors.affiliation: ADx NeuroSciences, Gent, Belgium.
authors.forename: Hugo
authors.initials: H
authors.lastname: Vanderstichele
authors.affiliation: Neurochemistry Laboratory, Department of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Teunissen
mesh_terms: D000327:Adsorption; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid* / Q000737:chemistry; D015415:Biomarkers / Q000134:cerebrospinal fluid; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016014:Linear Models; D010446:Peptide Fragments / Q000134:cerebrospinal fluid* / Q000737:chemistry; D000073623:Pre-Analytical Phase / Q000295:instrumentation; D011795:Surveys and Questionnaires; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)
keywords: Adsorption; Alzheimer's disease; Amyloid β (1–40); Amyloid β (1–42); Biobanking; Biomarkers; Cerebrospinal fluid; Preanalytical variation; Ratio Aβ(42)/Aβ(40)