title: Identification of brain cell death associated proteins in human post-mortem cerebrospinal fluid.
abstract: Following any form of brain insult, proteins are released from damaged tissues into the cerebrospinal fluid (CSF). This body fluid is therefore an ideal sample to use in the search for biomarkers of neurodegenerative disorders and brain damage. In this study, we used human post-mortem CSF as a model of massive brain injury and cell death for the identification of such protein markers. Pooled post-mortem CSF samples were analyzed using a protocol that combined immunoaffinity depletion of abundant CSF proteins, off-gel electrophoresis, SDS-PAGE and protein identification by LC-MS/MS. A total of 299 proteins were identified, of which 172 proteins were not previously described to be present in CSF. Of these 172 proteins, more than 75% have been described as intracellular proteins suggesting that they were released from damaged cells. Immunoblots of a number of proteins were performed on individual post-mortem CSF samples and confirmed elevated concentrations in post-mortem CSF compared to ante-mortem CSF. Interestingly, among the proteins specifically identified in the post-mortem CSF, several have been previously described as biochemical markers of brain damage.
authors.affiliation: Biomedical Proteomics Research Group, Department of Structural Biology and Bioinformatics, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Burgess
authors.forename: Pierre
authors.initials: P
authors.lastname: Lescuyer
authors.forename: Alexandre
authors.initials: A
authors.lastname: Hainard
authors.forename: Pierre R
authors.initials: PR
authors.lastname: Burkhard
authors.forename: Natacha
authors.initials: N
authors.lastname: Turck
authors.forename: Philippe
authors.initials: P
authors.lastname: Michel
authors.forename: Joël S
authors.initials: JS
authors.lastname: Rossier
authors.forename: Frédéric
authors.initials: F
authors.lastname: Reymond
authors.forename: Denis F
authors.initials: DF
authors.lastname: Hochstrasser
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Sanchez
mesh_terms: D015415:Biomarkers / Q000134:cerebrospinal fluid; D001930:Brain Injuries / Q000473:pathology*; D016923:Cell Death; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis* / Q000145:classification; D006801:Humans; D019636:Neurodegenerative Diseases / Q000134:cerebrospinal fluid; D011506:Proteins / Q000737:chemistry* / Q000145:classification; D040901:Proteomics / Q000379:methods
chemical_list: D015415:Biomarkers; D002556:Cerebrospinal Fluid Proteins; D011506:Proteins