Abstract
BackgroundStudies in animals suggest that the noradrenergic system arising from the locus coeruleus (LC) and dopaminergic pathways mutually influence each other. Little is known however, about the functional state of the LC in patients with Parkinson disease (PD).MethodsWe retrospectively reviewed clinical and imaging data of 94 subjects with PD at an early clinical stage (Hoehn and Yahr stage 1-2) who underwent single photon computed tomography imaging with FP-CIT ([123I] N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) tropane). FP-CIT binding values from the patients were compared with 15 healthy subjects: using both a voxel-based whole brain analysis and a volume of interest analysis of a priori defined brain regions.ResultsAverage FP-CIT binding in the putamen and caudate nucleus was significantly reduced in PD subjects (43% and 57% on average, respectively; p < 0.001). In contrast, subjects with PD showed an increased binding in the LC (166% on average; p < 0.001) in both analyses. LC-binding correlated negatively with striatal FP-CIT binding values (caudate: contralateral, ρ = -0.28, p < 0.01 and ipsilateral ρ = -0.26, p < 0.01; putamen: contralateral, ρ = -0.29, p < 0.01 and ipsilateral ρ = -0.29, p < 0.01).ConclusionsThese findings are consistent with an up-regulation of noradrenaline reuptake in the LC area of patients with early stage PD, compatible with enhanced noradrenaline release, and a compensating activity for degeneration of dopaminergic nigrostriatal projections.
Highlights
Studies in animals suggest that the noradrenergic system arising from the locus coeruleus (LC) and dopaminergic pathways mutually influence each other
Clinical inclusion criteria for subjects with Parkinson disease (PD) were: (a) diagnosis according to the UK Parkinson Disease Brain Bank criteria; (b) absence of any signs indicative for atypical parkinsonism over a follow-up period of at least three years after symptoms onset; (c) Hoehn and Yahr (H&Y) stage 1 or 2 in drugs-off state at the time of SPECT; (d) positive clinical improvement at Unified Parkinson Disease Rating Scale (UPDRS) after L-Dopa intake (i.e. > 30% from drug-off state) at some point during the three years of follow up; (e) a normal Magnetic Resonance Imaging (MRI)
Increased FP-CIT binding in the LC area The present study provides in vivo evidence of higher baseline catecholamine transporter binding in the LC region in a large and homogeneous cohort of subjects with early PD
Summary
Studies in animals suggest that the noradrenergic system arising from the locus coeruleus (LC) and dopaminergic pathways mutually influence each other. About the functional state of the LC in patients with Parkinson disease (PD). The LC-NA system and noradrenaline molecular transporters (NET) should be investigated in vivo by dedicated, highly specific radiotracers displaying low background non-NET binding, high sensitivity to variations in NET density and fast kinetics. As such a radiotracer is not available for large clinical studies, [13] we employed single photon computed tomography (SPECT) with FP-CIT ([123I] N-ω-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) tropane) in a large, homogeneous cohort of early stage PD patients. When applied to an anatomical region with known low dopamine reuptake transporter capacity such as the LC, it allows investigation of the NA-dependent synaptic activity
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