Objective: We aimed to determine whether the risk of Parkinson’s disease (PD) is increased in patients with Moyamoya disease (MMD) and to identify the potential role of RNF213 gene.

Background: MMD is a rare cerebrovascular disorder marked by the progressive narrowing of arteries at the base of the brain and forming abnormal collateral vascular networks. While vascular parkinsonism is noted in MMD, its link to Parkinson’s disease PD has not been explored.

Method: We report two cases of PD with a history of MMD associated with the Arg4810Lys variant of RNF213. Using the Korean National Health Insurance Service database, we studied the association between MMD and subsequent PD risk using Cox proportional hazards regression analysis. Moreover, we explored the interaction between α-synuclein and RNF213 proteins by overexpressing SNCA and RNF213 in SH-SY5Y cells. Furthermore, we confirmed the proximity of Lewy pathology and RNF213 proteins in postmortem brain tissues from three patients with PD and age-matched controls.

Results: From 16,830 patients with MMD aged ≥40, 3,415 were enrolled excluding those with previous PD or stroke, alongside a matched control group of 33,974. The analysis revealed an increased PD risk in patients with MMD (hazard ratio=4.45 [3.40-5.82], p<0.0001). RNF213 overexpression led to cytoplasmic inclusions, exacerbated by co-expression of SNCA and the Arg4810Lys variant of RNF213. Histological studies confirmed the co-localization of α-synuclein aggregates and RNF213 proteins in PD brain tissues.

Conclusion: This study confirms the heightened PD risk in patients with MMD and suggests a pathophysiological link through α-synuclein and RNF213 interactions.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/moyamoya-disease-and-the-risk-of-parkinsons-disease/