title: GBA-associated parkinsonism and dementia: beyond α-synucleinopathies?
abstract: OBJECTIVE
  To date the role of GBA mutations beyond α-synucleinopathies in the parkinsonism-dementia spectrum is still unclear. The aim of the study was to screen for GBA mutations in progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), primary progressive aphasia (PPA) and the behavioural variant of frontotemporal dementia (bvFTD).
  
  
  METHODS
  In all, 303 patients with a clinical diagnosis of PSP (n = 157), CBS (n = 39), PPA (n = 35) and bvFTD (n = 72) and 587 neurologically healthy controls were screened for the most common GBA mutations.
  
  
  RESULTS
  GBA mutations were detected in one healthy control and four patients with a clinical diagnosis of PSP (n = 1), probable CBS (n = 2) and PPA (n = 1, with concomitant C9orf72 expansion). Overall the prevalence of GBA mutations was low in non-α-synucleinopathies but significantly higher in the CBS subgroup compared to controls.
  
  
  CONCLUSIONS
  Although numbers are small, our findings indicate that the clinical phenotype of GBA-associated neurodegenerative disease is more heterogeneous than previously assumed, including phenotypes not usually associated with underlying α-synucleinopathies. This may be of relevance, once causal therapeutic strategies for GBA-associated neurodegenerative disease are developed.
authors.affiliation: Center of Neurology, Hertie Institute for Clinical Brain Research, Department of Neurodegeneration, University of Tübingen, Tübingen, Germany.|Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Pilotto
authors.affiliation: Center of Neurology, Hertie Institute for Clinical Brain Research, Department of Neurodegeneration, University of Tübingen, Tübingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Schulte
authors.affiliation: Center of Neurology, Hertie Institute for Clinical Brain Research, Department of Neurodegeneration, University of Tübingen, Tübingen, Germany.
authors.forename: A K
authors.initials: AK
authors.lastname: Hauser
authors.affiliation: Center of Neurology, Hertie Institute for Clinical Brain Research, Department of Neurodegeneration, University of Tübingen, Tübingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen, Germany.|CeGaT GmbH, Tübingen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Biskup
authors.affiliation: Center of Neurology, Hertie Institute for Clinical Brain Research, Department of Neurodegeneration, University of Tübingen, Tübingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Munz
authors.affiliation: Center of Neurology, Hertie Institute for Clinical Brain Research, Department of Neurodegeneration, University of Tübingen, Tübingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Brockmann
authors.affiliation: Center of Neurology, Hertie Institute for Clinical Brain Research, Department of Neurodegeneration, University of Tübingen, Tübingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Schaeffer
authors.affiliation: Center of Neurology, Hertie Institute for Clinical Brain Research, Department of Neurodegeneration, University of Tübingen, Tübingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Synofzik
authors.affiliation: Center of Neurology, Hertie Institute for Clinical Brain Research, Department of Neurodegeneration, University of Tübingen, Tübingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Maetzler
authors.affiliation: Center of Neurology, Hertie Institute for Clinical Brain Research, Department of Neurodegeneration, University of Tübingen, Tübingen, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Suenkel
authors.affiliation: Center of Neurology, Hertie Institute for Clinical Brain Research, Department of Neurodegeneration, University of Tübingen, Tübingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Srulijes
authors.affiliation: Center of Neurology, Hertie Institute for Clinical Brain Research, Department of Neurodegeneration, University of Tübingen, Tübingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Gasser
authors.affiliation: Center of Neurology, Hertie Institute for Clinical Brain Research, Department of Neurodegeneration, University of Tübingen, Tübingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Berg
mesh_terms: D000368:Aged; D018888:Aphasia, Primary Progressive / Q000235:genetics* / Q000503:physiopathology; D001480:Basal Ganglia Diseases / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics* / Q000503:physiopathology; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D013494:Supranuclear Palsy, Progressive / Q000235:genetics / Q000503:physiopathology
chemical_list: D005962:Glucosylceramidase
keywords: C9orf72 expansion; GBA; corticobasal syndrome; frontotemporal dementia; primary progressive aphasia; progressive supranuclear palsy