Introduction
Epidemiological studies have demonstrated that tobacco smoking is associated with a lower incidence of Parkinson's disease (PD, 2 ). As suggested by in vitro und in vivo animal studies nicotine seems to be a neuroprotective factor. The alpha4beta2-subunits of the nAChR, on which nicotine binds with its highest affinity seem to be involved. By using the radioligand 2-[18F]F-A-85380 and positron emission tomography (PET) we tested the hypothesis whether these receptors are altered in patients with PD 1 .
Methods
Seven patients with PD (39–70 yrs), different clinical severity (UPDRS-III: 8-49, MMSE: 23–29), with symptomatic therapy and 5 age-matched normal subjects (37–64 yrs) were measured following a short-time infusion (90 s) of the radioligand 2-[18F]F-A-85380 using PET (Siemens ECAT EXACT HR+, Germany) over a time period of 7 hours. Parametric images of the distribution volumes DV [mL/ccm] for 2-FA were calculated by Logan plot after correction of the arterial input function for plasma protein binding and radioactive metabolites. After co-registration with the individual MRI (Hermes Medical Solutions, Sweden), DVs in 23 ROIs (7 subcortical, 16 cortical) were analyzed. The binding potential BP=DV/DV corpus callosum -1 was calculated. In addition, the dopamine transporter (DAT)-availability in the basal ganglia was assessed using [123I]-FP-CIT-SPECT.
Results
In the patients with PD, 2-[18F]F-A-85380-BP decreases were found in the left caudate nucleus (−43.8%, p<0.05). There was a tendency for a decreased BP in the right caudate nucleus (−20.5%), in the left putamen (−13.2%), in pons (−5.9%) and in the cerebellum (−6.9%). There was a tendency for an increased BP in the thalamus, in the hippocampus and in the substantia nigra (+6.7%).
Conclusions
This preliminary data strongly suggest an alteration of alpha4beta2 nAChRs availability in PD. This might be regional different (decreased in left caudate nucleus, in the basal ganglia, pons and cerebellum, increased in the thalamus, hippocampus and in the substantia nigra). Whereas the regional decrease of the alpha4beta2 nAChRs is in agreement with post mortem studies in PD, the increased availability of the alpha4beta2 nAChRs could represent a denervation supersensitivity. Further investigation in a larger group of patients is underway.