Effects of blood contamination and the rostro-caudal gradient on the human cerebrospinal fluid proteome

Elise Aasebø; Jill Anette Opsahl; Yngvild Bjørlykke; Kjell-Morten Myhr; Ann Cathrine Kroksveen; Frode S Berven

doi:10.1371/journal.pone.0090429

Effects of blood contamination and the rostro-caudal gradient on the human cerebrospinal fluid proteome

PLoS One. 2014 Mar 5;9(3):e90429. doi: 10.1371/journal.pone.0090429. eCollection 2014.

Authors

Elise Aasebø¹, Jill Anette Opsahl¹, Yngvild Bjørlykke², Kjell-Morten Myhr³, Ann Cathrine Kroksveen¹, Frode S Berven⁴

Affiliations

¹ Proteomics Unit (PROBE), Department of Biomedicine, University of Bergen, Bergen, Norway; The KG Jebsen Centre for MS-research, Department of Clinical Medicine, University of Bergen, Bergen, Norway.
² Department of Clinical Science, University of Bergen, Bergen, Norway.
³ The KG Jebsen Centre for MS-research, Department of Clinical Medicine, University of Bergen, Bergen, Norway; The Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Bergen, Norway.
⁴ Proteomics Unit (PROBE), Department of Biomedicine, University of Bergen, Bergen, Norway; The KG Jebsen Centre for MS-research, Department of Clinical Medicine, University of Bergen, Bergen, Norway; The Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Bergen, Norway.

Abstract

Over the last years there has been an increased focus on the importance of knowing the effect of pre-analytical influence on the proteomes under study, particularly in the field of biomarker discovery. We present three proteomics studies examining the effect of blood contamination and the rostro-caudal gradient (RCG) on the cerebrospinal fluid (CSF) proteome, in addition to plasma/CSF protein ratios. The studies showed that the central nervous system (CNS) derived proteins appeared to be unaffected by the RCG, while the plasma-derived proteins showed an increase in concentration towards the lumbar area. This implies that the concentration of the plasma-derived proteins in CSF will vary depending on the volume of CSF that is collected. In the CSF samples spiked with blood, 262 of 814 quantified proteins showed an abundance increase of more than 1.5 fold, while 403 proteins had a fold change of less than 1.2 and appeared to be unaffected by blood contamination. Proteins with a high plasma/CSF ratio appeared to give the largest effect on the CSF proteome upon blood contamination. The results give important background information on how factors like blood contamination, RCG and blood-CNS-barrier influences the CSF proteome. This information is particularly important in the field of biomarker discovery, but also for routine clinical measurements. The data from the blood contamination and RCG discovery studies have been deposited to the ProteomeXchange with identifier PXD000401.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Artifacts
Blood Proteins / cerebrospinal fluid*
Blood Proteins / isolation & purification
Cerebrospinal Fluid Proteins / isolation & purification
Cerebrospinal Fluid Proteins / metabolism*
Chromatography, Ion Exchange
Chromatography, Reverse-Phase
Humans
Proteome / isolation & purification
Proteome / metabolism
Spinal Puncture
Supranuclear Palsy, Progressive / cerebrospinal fluid*

Substances

Blood Proteins
Cerebrospinal Fluid Proteins
Proteome

Grants and funding

The study was supported by the National Program for Research in Functional Genomics (FUGE) funded by the Norwegian Research Council, Western Norway Regional Health Authority, the Meltzer Foundation, Kjell Alme's Legacy for Research in Multiple Sclerosis, and the Kristian Gerhard Jebsen Foundation. The data deposition to the ProteomeXchange Consortium was supported by PRIDE Team, EBI. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.