ABSTRACT
Postmortem data indicate loss of serotoninergic neurons in Parkinson's disease (PD). We used the serotonin transporter (SERT) radioligand 3-amino-4-(2-dimethylaminomethyl-phenylsulfaryl)-benzonitril (DASB) and positron emission tomography to examine SERT distribution and changes in early PD subjects. We studied five PD subjects (H&Y 1 to 2.5) and eight normal controls. There is reduced SERT binding in PD. The magnitude of DASB binding reductions was greater in the forebrain than in the brainstem regions. There was no asymmetry of diminished SERT binding. DASB binding in the medulla was relatively spared, inconsistent with the description of early prominent pathologic study in these caudal brainstem nuclei.
Subject(s)
Brain Stem/chemistry , Parkinson Disease/metabolism , Serotonin Plasma Membrane Transport Proteins/analysis , Adult , Aged , Brain Chemistry , Brain Stem/pathology , Case-Control Studies , Female , Humans , Male , Medulla Oblongata/chemistry , Medulla Oblongata/pathology , Middle Aged , Nerve Tissue Proteins , Parkinson Disease/pathology , Positron-Emission Tomography , Prosencephalon/chemistry , Prosencephalon/pathology , Protein Binding/physiology , Radioligand Assay , Serotonin Plasma Membrane Transport Proteins/metabolism , Time FactorsABSTRACT
The type-2 vesicular monoamine transporter (VMAT2) might serve as an objective biomarker of Parkinson disease (PD) severity. Thirty-one subjects with early-stage PD and 75 normal subjects underwent continuous intravenous infusion of (+)-[(11)C]dihydrotetrabenazine (DTBZ) and positron emission tomography (PET) imaging to estimate the striatal VMAT2 binding site density with equilibrium tracer modeling. Parkinson disease patients were evaluated clinically in the practically defined 'off' state with the Unified Parkinson Disease Rating Scale (UPDRS), the Hoehn and Yahr Scale (HY), and the Schwab and England Activities of Daily Living Scale (SE). In normal subjects there was age-related decline in striatal DTBZ binding, approximating 0.5% per year. In PD subjects, specific DTBZ binding was reduced in the caudate nucleus (CD; -44%), anterior putamen (-68%), and posterior putamen (PP; -77%). The PP-to-CD ratio of binding was reduced significantly in PD subjects. Dihydrotetrabenazine binding was also reduced by approximately 50% in the PD substantia nigra. Striatal binding reductions correlated significantly with PD duration and SE scores, but not with HY stage or with UPDRS motor subscale (UPDRS(III)) scores. Striatal and midbrain DTBZ binding was asymmetric in PD subjects, with greatest reductions contralateral to the most clinically affected limbs. There was significant correlation between asymmetry of DTBZ binding and clinical asymmetry measured with the UPDRS(III). In HY stage 1 and 1.5 subjects (n=16), PP DTBZ binding contralateral to the clinically unaffected body side was reduced by 73%, indicating substantial preclinical nigrostriatal pathology in PD. We conclude that (+)-[(11)C]DTBZ-PET imaging displays many properties necessary of a PD biomarker.
Subject(s)
Aging/metabolism , Biogenic Monoamines/metabolism , Parkinson Disease/diagnostic imaging , Parkinson Disease/metabolism , Synaptic Vesicles/metabolism , Adult , Aged , Aged, 80 and over , Algorithms , Female , Humans , Male , Middle Aged , Neostriatum/diagnostic imaging , Neostriatum/metabolism , Positron-Emission Tomography , Radiopharmaceuticals , Tetrabenazine/analogs & derivatives , Tetrabenazine/pharmacokinetics , Vesicular Monoamine Transport Proteins/metabolismABSTRACT
Striatal dysfunction is thought to underlie many dystonias. We used [(123)I]iodobenzovesamicol single-photon emission computed tomography imaging to determine the density of cholinergic terminals in the striatum and other brain regions in 13 subjects with idiopathic cervical dystonia. Striatal [(131)I]iodobenzovesamicol binding was reduced. These results support a role for striatal dysfunction in idiopathic dystonias and suggest diminished striatal cholinergic interneuron density in cervical dystonia.
