Abstract
Analysis of cerebrospinal fluid (CSF) is important for diagnosis of neurological diseases. Especially for neurodegenerative diseases, abnormal protein abundance in CSF is an important biomarker. However, the quality of CSF is a key factor for the analytic outcome. Any external contamination has tremendous impact on the analysis and the reliability of the results. In this study, we evaluated the effect of blood contamination in CSF with respect to protein biomarker identification. We compared three distinct measures: Combur10-Test® strips, a specific hemoglobin ELISA, and bottom-up mass spectrometry (MS)-based proteomics for the determination of the general blood contamination level. In parallel, we studied the impact of blood contamination on the detectability of alpha-synuclein (aSyn), a highly abundant protein in blood/erythrocytes and a potential biomarker for Parkinson’s disease. Comparable results were achieved, with all three approaches enabling detection of blood levels in CSF down to 0.001%. We found higher aSyn levels with increasing blood contamination, highlighting the difficulty of authentic quantification of this protein in CSF. Based on our results, we identified other markers for blood contamination beyond hemoglobin and defined a grading system for blood levels in CSF samples, including a lower limit of tolerable blood contamination for MS-based biomarker studies.
Highlights
Cerebrospinal fluid (CSF) is one of the main sources for the discovery of biomarkers in the field of central nervous system diseases
We found that the Combur10-Test® and mass spectrometry (MS) analysis were useful approaches to detect blood contamination down to a level of 0.001%, which is below the recommended cut-off value of
We evaluated the performance of urine reagent test strips for the detection of blood-contaminated CSF prior to mass spectrometry (MS)-based analysis as a fast and cost-effective approach alongside the currently performed RBC count in clinical laboratories
Summary
Cerebrospinal fluid (CSF) is one of the main sources for the discovery of biomarkers in the field of central nervous system diseases It is produced in the choroidal plexus and surrounds the brain as well as the spinal cord; CSF is in direct contact with the central nervous system. CSF is collected by routine lumbar punctures During this procedure, unwanted vascular bleeding may occur, causing peripheral blood to contaminate CSF, which happens in up to 20% of standard lumbar punctures [1]. Those blood contaminations can introduce variabilities affecting reliable detection and/or measurement of biomarkers such as alpha-synuclein (aSyn) or routine CSF results like total protein measurements, as well as blood-CSF barrier function [2,3]. ASyn has been shown to be highly aggregated in the brains of Parkinson’s disease (PD)
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