title: Identification of brain-enriched proteins in the cerebrospinal fluid proteome by LC-MS/MS profiling and mining of the Human Protein Atlas.
abstract: BACKGROUND
  Cerebrospinal fluid (CSF) is a proximal fluid which communicates closely with brain tissue, contains numerous brain-derived proteins and thus represents a promising fluid for discovery of biomarkers of central nervous system (CNS) diseases. The main purpose of this study was to generate an extensive CSF proteome and define brain-related proteins identified in CSF, suitable for development of diagnostic assays.
  
  
  METHODS
  Six non-pathological CSF samples from three female and three male individuals were selected for CSF analysis. Samples were first subjected to strong cation exchange chromatography, followed by LC-MS/MS analysis. Secreted and membrane-bound proteins enriched in the brain tissues were retrieved from the Human Protein Atlas.
  
  
  RESULTS
  In total, 2615 proteins were identified in the CSF. The number of proteins identified per individual sample ranged from 1109 to 1421, with inter-individual variability between six samples of 21 %. Based on the Human Protein Atlas, 78 brain-specific proteins found in CSF samples were proposed as a signature of brain-enriched proteins in CSF.
  
  
  CONCLUSIONS
  A combination of Human Protein Atlas database and experimental search of proteins in specific body fluid can be applied as an initial step in search for disease biomarkers specific for a particular tissue. This signature may be of significant interest for development of novel diagnostics of CNS diseases and identification of drug targets.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON Canada ; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON Canada.
authors.forename: Ilijana
authors.initials: I
authors.lastname: Begcevic
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON Canada ; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON Canada ; Department of Clinical Biochemistry, University Health Network, Toronto, ON Canada.
authors.forename: Davor
authors.initials: D
authors.lastname: Brinc
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON Canada ; Department of Clinical Biochemistry, University Health Network, Toronto, ON Canada.
authors.forename: Andrei P
authors.initials: AP
authors.lastname: Drabovich
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON Canada.
authors.forename: Ihor
authors.initials: I
authors.lastname: Batruch
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON Canada ; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON Canada ; Department of Clinical Biochemistry, University Health Network, Toronto, ON Canada.
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Diamandis
keywords: Brain-enriched proteins; Cerebrospinal fluid; Human Protein Atlas; LC-MS/MS; Mass spectrometry