title: Expanding the cerebrospinal fluid endopeptidome.
abstract: Biomarkers of neurodegenerative disorders are needed to assist in diagnosis, to monitor disease progression and therapeutic interventions, and to provide insight into disease mechanisms. One route to identify such biomarkers is by proteomic and peptidomic analysis of cerebrospinal fluid (CSF). In the current study, we performed an in-depth analysis of the human CSF endopeptidome to establish an inventory that may serve as a basis for future targeted biomarker studies. High-pH RP HPLC was employed for off-line sample prefractionation followed by low-pH nano-LC-MS analysis. Different software programs and scoring algorithms for peptide identification were employed and compared. A total of 18 031 endogenous peptides were identified at a FDR of 1%, increasing the number of known endogenous CSF peptides 10-fold compared to previous studies. The peptides were derived from 2 053 proteins of which more than 60 have been linked to neurodegeneration. Notably, among the findings were six peptides derived from microtubule-associated protein tau, three of which span the diagnostically interesting threonine-181 (Tau-F isoform). Also, 213 peptides from amyloid precursor protein were identified, 58 of which were partially or completely within the sequence of amyloid β 1-40/42, as well as 109 peptides from apolipoprotein E, spanning sequences that discriminate between the E2/E3/E4 isoforms of the protein.
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
authors.forename: Karl T
authors.initials: KT
authors.lastname: Hansson
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.|Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
authors.forename: Tobias
authors.initials: T
authors.lastname: Skillbäck
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
authors.forename: Elin
authors.initials: E
authors.lastname: Pernevik
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.|Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
authors.forename: Silke
authors.initials: S
authors.lastname: Kern
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.|Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Portelius
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.|Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
authors.forename: Kina
authors.initials: K
authors.lastname: Höglund
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Brinkmalm
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
authors.forename: Jessica
authors.initials: J
authors.lastname: Holmén-Larsson
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.|Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.|Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.|Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.|Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Gobom
mesh_terms: D015415:Biomarkers / Q000134:cerebrospinal fluid; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis*; D002853:Chromatography, Liquid / Q000379:methods; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D019636:Neurodegenerative Diseases / Q000134:cerebrospinal fluid; D010455:Peptides / Q000134:cerebrospinal fluid*; D040901:Proteomics / Q000379:methods*; D012984:Software
chemical_list: D015415:Biomarkers; D002556:Cerebrospinal Fluid Proteins; D010455:Peptides
keywords: Alzheimer's disease; Biomarkers; Cerebrospinal fluid; Neurodegeneration; Peptidomics