Objective: To investigate the relationship between tremor and α4β2 nicotinic cholinergic receptor (nAChR) expression in brain regions associated with tremor in Parkinson’s disease (PD), including the substantia nigra, putamen, thalamus, premotor cortex, cerebellar hemisphere and vermis.

Background: Anticholinergic agents are effective against tremor in many PD patients. Cholinergic system changes may play a role in the pathophysiology of PD tremor.

Methods: PD patients (N=19) [7 Female; 67.7±8.3 (52-88) years old; 5.9±3.4 (1-16) years motor disease duration, HY stages 2-3, MOCA score 27.6±2.2 (22-30); MDS-UPDRS motor score 43.7±15.4 (20.5-74)] underwent [18F]flubatine α4β2 nicotinic receptor PET imaging. MDS-UPDRS motor assessment was performed in the dopaminergic “off” state. Tremor severity was based on the MDS-UPDRS sub-scores for tremor.

Results: The mean MDS-UPDRS tremor sub-score was 8.5±4.6 (range 1-19.5). Stepwise linear regression with tremor score as the dependent variable showed a significant (F=6.5, p=0.021) positive association between α4β2 nAChR expression in substantia nigra and MDS-UPDRS tremor sub score (β=0.526, t=2.55, p=0.021). There was no significant association of tremor with MDS-UPDRS total motor score and disease duration or α4β2 nAChR expression in putamen, thalamus, premotor cortex, cerebellar hemisphere and vermis.

Conclusions: Increased α4β2 nAChR expression in the substantia nigra correlates with increased tremor in Parkinson’s disease. This finding may reflect changes in expression of α4β2 nAChRs by nigral neurons or by presynaptic pedunculopontine cholinergic afferent terminals. These results suggest that PD tremor is mediated by altered cholinergic signaling in the nigra.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/substantia-nigra-42-nicotinic-cholinergic-receptor-expression-correlates-with-tremor-in-parkinsons-disease/