A Pilotto1,2, C Schulte1,3, A K Hauser1, S Biskup1,3,4, M Munz1,3, K Brockmann1,3, E Schaeffer1,3, M Synofzik1,3, W Maetzler1,3, U Suenkel1, K Srulijes1,3, T Gasser1,3, D Berg1,3. 1. Center of Neurology, Hertie Institute for Clinical Brain Research, Department of Neurodegeneration, University of Tübingen, Tübingen, Germany. 2. Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy. 3. German Center for Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen, Germany. 4. CeGaT GmbH, Tübingen, Germany.
Abstract
BACKGROUND AND PURPOSE: 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. CONCLUSION: 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.
BACKGROUND AND PURPOSE: 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. CONCLUSION: 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: Andrew E Arrant; Jonathan R Roth; Nicholas R Boyle; Shreya N Kashyap; Madelyn Q Hoffmann; Charles F Murchison; Eliana Marisa Ramos; Alissa L Nana; Salvatore Spina; Lea T Grinberg; Bruce L Miller; William W Seeley; Erik D Roberson Journal: Acta Neuropathol Commun Date: 2019-12-23 Impact factor: 7.801