title: Identification of a biomarker in cerebrospinal fluid for neuronopathic forms of Gaucher disease.
abstract: Gaucher disease, a recessive inherited metabolic disorder caused by defects in the gene encoding glucosylceramidase (GlcCerase), can be divided into three subtypes according to the appearance of symptoms associated with central nervous system involvement. We now identify a protein, glycoprotein non-metastatic B (GPNMB), that acts as an authentic marker of brain pathology in neurological forms of Gaucher disease. Using three independent techniques, including quantitative global proteomic analysis of cerebrospinal fluid (CSF) in samples from Gaucher disease patients that display neurological symptoms, we demonstrate a correlation between the severity of symptoms and GPNMB levels. Moreover, GPNMB levels in the CSF correlate with disease severity in a mouse model of Gaucher disease. GPNMB was also elevated in brain samples from patients with type 2 and 3 Gaucher disease. Our data suggest that GPNMB can be used as a marker to quantify neuropathology in Gaucher disease patients and as a marker of treatment efficacy once suitable treatments towards the neurological symptoms of Gaucher disease become available.
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Hila
authors.initials: H
authors.lastname: Zigdon
authors.affiliation: de Botton Institute for Protein Profiling, The Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Alon
authors.initials: A
authors.lastname: Savidor
authors.affiliation: de Botton Institute for Protein Profiling, The Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Yishai
authors.initials: Y
authors.lastname: Levin
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Anna
authors.initials: A
authors.lastname: Meshcheriakova
authors.affiliation: Institute of Metabolic Disease, Baylor Research Institute, Dallas, TX, United States of America.
authors.forename: Raphael
authors.initials: R
authors.lastname: Schiffmann
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Futerman
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D000818:Animals; D015415:Biomarkers / Q000134:cerebrospinal fluid / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005776:Gaucher Disease / Q000134:cerebrospinal fluid* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000134:cerebrospinal fluid* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data
chemical_list: D015415:Biomarkers; C503042:GPNMB protein, human; D008562:Membrane Glycoproteins