In vivo assessment of brain monoamine systems in parkin gene carriers: A PET study

Abstract

PET studies in parkin-linked parkinsonism have generally been performed to assess striatal dopaminergic dysfunction and very little is known about the involvement of other monoaminergic structures in these patients. Measurements of (18)F-dopa uptake into serotonergic and noradrenergic structures provide an indication of the functional integrity of these nerve terminals. We used (18)F-dopa PET to assess changes in brain monoaminergic function associated with parkin mutations. Twelve patients with parkin-linked parkinsonism and 12 asymptomatic parkin heterozygotes were included in the study. Eleven healthy controls, 12 patients with idiopathic Parkinson's disease (IPD), and four patients with PINK1 mutations were also investigated for comparison. parkin patients and IPD patients were matched for striatal dopaminergic dysfunction, as measured by (18)F-dopa uptake. Compared to controls, parkin patients showed significant (18)F-dopa reductions in the caudate, putamen, ventral striatum, locus coeruleus, midbrain raphe, and pallidum. The same structures showed reduced uptake in IPD patients, who additionally had significant reductions in hypothalamus, ventral anterior thalamus, and pineal gland. Direct comparison of parkin with IPD patients showed that hypothalamus was targeted in IPD and midbrain raphe in parkin disease. Patients with PINK1 mutation and several parkin heterozygotes also showed monoaminergic dysfunction. These findings suggest that parkin patients and IPD patients with similar striatal dysfunction have different patterns of monoaminergic involvement, with more widespread dysfunction in IPD.