title: Ubiquitin: a potential cerebrospinal fluid progression marker in Huntington's disease.
abstract: BACKGROUND
  Finding early and dynamic biomarkers in Huntington's disease is a key to understanding the early pathology of Huntington's disease and potentially to tracking disease progression. This would benefit the future evaluation of potential neuroprotective and disease-modifying therapies, as well as aid in identifying an optimal time point for initiating a potential therapeutic intervention.
  
  
  METHODS
  This explorative proteomics study evaluated cerebrospinal fluid from 94 Huntington's disease gene-expansion carriers (39 premanifest and 55 manifest) and 27 Huntington's disease gene-expansion negative individuals using surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry. Differences in peak intensity from SELDI-TOF spectra were evaluated.
  
  
  RESULTS
  Levels of 10 peaks were statistically significantly different between manifest gene-expansion carriers and controls. One of them identified as ubiquitin was shown to be dependent on the Unified Huntington Disease Rating Scale Total Functional Capacity, a pseudo-measure of disease severity (P = 0.001), and the Symbol Digit Modalities Test (0.04) in manifest and CAG-age product score (P = 0.019) in all gene-expansion carriers.
  
  
  CONCLUSIONS
  Multiple studies have shown that the ubiquitin-proteasome system is involved in Huntington's disease pathogenesis and understanding of this involvement may have therapeutic potential in humans. This is the first study on cerebrospinal fluid to confirm the involvement of the ubiquitin-proteasome system in Huntington's disease. Furthermore it is shown that ubiquitin increases with disease progression and CAG-age product score and therefore may have the potential as a Huntington's disease progression marker, also prior to motor onset.
authors.affiliation: Department of Neurology, Danish Dementia Research Centre, Neurogenetics Clinic, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.|Department of Cellular and Molecular Medicine, Section of Neurogenetics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: T
authors.initials: T
authors.lastname: Vinther-Jensen
authors.affiliation: Department of Neurology, Danish Dementia Research Centre, Neurogenetics Clinic, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: A H
authors.initials: AH
authors.lastname: Simonsen
authors.affiliation: Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: E
authors.initials: E
authors.lastname: Budtz-Jørgensen
authors.affiliation: Department of Neurology, Danish Dementia Research Centre, Neurogenetics Clinic, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.|Department of Cellular and Molecular Medicine, Section of Neurogenetics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: L E
authors.initials: LE
authors.lastname: Hjermind
authors.affiliation: Department of Neurology, Danish Dementia Research Centre, Neurogenetics Clinic, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.|Department of Cellular and Molecular Medicine, Section of Neurogenetics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: J E
authors.initials: JE
authors.lastname: Nielsen
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid; D018450:Disease Progression; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D040901:Proteomics; D025801:Ubiquitin / Q000134:cerebrospinal fluid*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D025801:Ubiquitin
keywords: Huntington's disease; SELDI-TOF; biomarkers; cerebrospinal fluid; premanifest; ubiquitin