Eline Willemse1, Kees van Uffelen2, Britta Brix3, Sebastiaan Engelborghs4, Hugo Vanderstichele5, Charlotte Teunissen2. 1. 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. 2. Neurochemistry Laboratory, Department of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. 3. Neurodegenerative Diseases Department, EUROIMMUN Medizinische Labordiagnostika AG, Lübeck, Germany. 4. 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. 5. ADx NeuroSciences, Gent, Belgium.
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.
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.
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