title: Functional brain imaging in glucocerebrosidase mutation carriers with and without parkinsonism.
abstract: Mutations in the glucocerebrosidase gene (GBA) increase the risk for Parkinson's disease and are also associated with an earlier onset of the disease and an akinetic parkinsonian phenotype. To investigate the underlying pathogenesis of this condition, we assessed cerebral metabolism using positron emission tomography (PET) in GBA mutation carriers with and without parkinsonism. [(18)F]-fluorodeoxyglucose (FDG)-PET using a three-dimensional stereotactic surface projection analysis was used to measure the cerebral metabolic rates of glucose (CMRGlc) in a patient with parkinsonism and Gaucher disease (GD) and five subjects with a heterozygous GBA mutation, including three patients with parkinsonism and three asymptomatic carriers in comparison to 10 healthy controls in the same age range. Dopaminergic neuronal activity was investigated using [(11)C] CFT- and [(11)C] raclopride-PET. All GBA mutation carriers displayed a significant CMRGlc decrease in the supplemental motor area (SMA). The carriers with parkinsonism showed additional hypometabolism in the parietooccipital cortices. The CFT and raclopride PET images in the asymptomatic carriers demonstrated the CFT binding to be within normal values in the putamen and a significant increase was observed in the caudate nucleus while raclopride binding in the striatum was in the normal range. An advanced parkinsonian carrier showed decreased CFT binding and increased raclopride binding in the striatum. The decreased CMRGlc in the SMA was characteristic of the GBA mutation carriers. The hypometabolism in the SMA may, therefore, be involved in the clinical characteristics of parkinsonism associated with GBA mutations when the carriers manifest parkinsonism.
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Handayama, Hamamatsu, Japan. satokono@hama-med.ac.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kono
authors.forename: Yasuomi
authors.initials: Y
authors.lastname: Ouchi
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Terada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ida
authors.forename: Makiko
authors.initials: M
authors.lastname: Suzuki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Miyajima
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging* / Q000503:physiopathology; D001931:Brain Mapping; D005260:Female; D005776:Gaucher Disease / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D009154:Mutation; D009474:Neurons / Q000000981:diagnostic imaging; D009483:Neuropsychological Tests; D020734:Parkinsonian Disorders / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000503:physiopathology; D049268:Positron-Emission Tomography
chemical_list: D005962:Glucosylceramidase