Missense variants in leucine-rich repeat kinase 2 (LRRK2) lead to familial and sporadic Parkinson’s disease (PD). The pathological features of PD patients with LRRK2 variants differ. Here, we report an autopsy case harboring the LRRK2 G2385R, a risk variant for PD occurring mainly in Asian populations. The patient exhibited levodopa-responsive parkinsonism at the early stage and visual hallucinations at the advanced stage. The pathological study revealed diffuse Lewy bodies with neurofibrillary tangles, amyloid plaques, and mild signs of neuroinflammation. Biochemically, detergent-insoluble phospho-α-synuclein was accumulated in the frontal, temporal, entorhinal cortexes, and putamen, consistent with the pathological observations. Elevated phosphorylation of Rab10, a substrate of LRRK2, was also prominent in various brain regions. In conclusion, G2385R appears to increase LRRK2 kinase activity in the human brain, inducing a deleterious brain environment that causes Lewy body pathology.

富含亮氨酸的重复激酶 2 (LRRK2)中的错义变体导致家族性和散发性帕金森病（PD）。具有 LRRK2 变异的 PD 患者的病理特征不同。在这里，我们报告了一个含有 LRRK2 G2385R 的尸检病例，这是一种主要发生在亚洲人群中的 PD 风险变异。患者早期表现出左旋多巴反应性帕金森综合征，晚期出现幻视。病理学研究显示弥漫性路易体具有神经原纤维缠结、淀粉样斑块和轻度神经炎症迹象。生化上，去污剂不溶性磷酸-α-突触核蛋白在额叶、颞叶、内嗅皮层和壳核中积累，与病理观察结果一致。Rab10（LRRK2 的底物）的磷酸化升高在大脑的各个区域也很突出。综上所述，