GBA-associated parkinsonism and dementia: beyond α-synucleinopathies?

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.