Objective: We investigated α4β2 acetylcholin receptor (nAChR) density in subjects with Parkinson’s disease (PD) with and without levodopa-induced dyskinesia (LID) and its correlation with dopaminergic striatal innervation and baseline brain metabolic activity.

Background: Levodopa induced dyskinesia (LID) are involuntary movements, that may occur during levodopa therapy in PD patients. Preliminary findings in primates showed that nicotinergic nAChR desensitization and/or down regulation by nicotine or nicotine antagonist can modulate striatal dopamine release and ameliorate LID.

Methods: We investigated 15 subjects with PD and LID (LID+, 8 M; age: 61.1±9.7 years; disease duration: 11.5±2.4 years; UPDRS-III: 19.5±11.4; UPDRS-IV > 2; LEDD = 900±278 mg) and a second group of 11 patients without LID (LID-, 9 M; age 67.3±7.6 years; disease duration: 7.5±3.9 years, UPDRS-III: 22.5±9.5; UPDRS-IV = 0; LEDD = 714±459 mg). Cognitive impairment and depression were excluded according to Mattis Dementia Rating Scale and Beck Depression Inventory. SPECT or PET with 5-[123I]Iodo-3-[2(S)-2-azetidinylmethoxy]pyridin and N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) tropane (in 13 LID+ and 9 LID-) or 18F-fluorodeoxyglucose (FDG) (in 12 LID+ and 9 LID-) were applied to measure nAChRs and DAT density or brain metabolism, respectively. Semiquantitative analysis was performed to calculate the (non-) specific binding potential of SPECT data using the software package PMOD. Statistical Parametric Mapping (SPM) was used to compare FDG uptake between PD cohorts.

Results: In LID+, we found a selective higher nAChRs density in the caudate nucleus with lower DAT binding potential (1.03±0.19 vs. 0.80±0.26, p<0.05, Wilcoxon test). No difference for nAChRs density was described when comparing all other brain regions. The nAChRs and DAT density correlated only in the caudate nuclei (Spearman’s ρ=0.57; p=0.01) of LID-, but not LID+. SPM analysis did not show any difference between baseline metabolic activity of PD with and without LID.

Conclusions: This study confirms a role of the cholinergic system in the pathophysiology of LID. We speculate a compensatory (upregulated) overexpression of nAChRs and/or a relatively preserved physiologic cholinergic activity despite neuronal degeneration in dyskinetic PD patients.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/levodopa-induced-dyskinesia-and-nicotinergic-42-acetylcholin-receptor-density-a-multi-tracer-imaging-study/