Mutations in GBA, the gene encoding glucocerebrosidase, the enzyme deficient in 
Gaucher disease, are common risk factors for Parkinson disease, as patients with 
Parkinson disease are over five times more likely to carry GBA mutations than 
healthy controls. Patients with GBA mutations generally have an earlier onset of 
Parkinson disease and more cognitive impairment than those without GBA 
mutations. We investigated whether GBA mutations alter the neurobiology of 
Parkinson disease, studying brain dopamine synthesis and resting regional 
cerebral blood flow in 107 subjects (38 women, 69 men). We measured dopamine 
synthesis with (18)F-fluorodopa positron emission tomography, and resting 
regional cerebral blood flow with H(2)(15)O positron emission tomography in the 
wakeful, resting state in four study groups: (i) patients with Parkinson disease 
and Gaucher disease (n = 7, average age = 56.6 ± 9.2 years); (ii) patients with 
Parkinson disease without GBA mutations (n = 11, 62.1 ± 7.1 years); (iii) 
patients with Gaucher disease without parkinsonism, but with a family history of 
Parkinson disease (n = 14, 52.6 ± 12.4 years); and (iv) healthy GBA-mutation 
carriers with a family history of Parkinson disease (n = 7, 50.1 ± 18 years). We 
compared each study group with a matched control group. Data were analysed with 
region of interest and voxel-based methods. Disease duration and Parkinson 
disease functional and staging scores were similar in the two groups with 
parkinsonism, as was striatal dopamine synthesis: both had greatest loss in the 
caudal striatum (putamen Ki loss: 44 and 42%, respectively), with less reduction 
in the caudate (20 and 18% loss). However, the group with both Parkinson and 
Gaucher diseases showed decreased resting regional cerebral blood flow in the 
lateral parieto-occipital association cortex and precuneus bilaterally. 
Furthermore, two subjects with Gaucher disease without parkinsonian 
manifestations showed diminished striatal dopamine. In conclusion, the pattern 
of dopamine loss in patients with both Parkinson and Gaucher disease was similar 
to sporadic Parkinson disease, indicating comparable damage in midbrain neurons. 
However, H(2)(15)O positron emission tomography studies indicated that these 
subjects have decreased resting activity in a pattern characteristic of diffuse 
Lewy body disease. These findings provide insight into the pathophysiology of 
GBA-associated parkinsonism.