Beck Goichi, Yamadera Misaki, Tarutani Airi, Yonenobu Yuki, Mike Asako, Hideshima Makoto, Kanki Hideaki, Maeda Kenichiro, Inoue Kimiko, Satake Wataru, Hasegawa Masato, Mochizuki Hideki, Murayama Shigeo
Department of Neurology, The University of Osaka Graduate School of Medicine, Suita, Japan.
Department of Pathology, NHO Osaka Toneyama Medical Center, Toyonaka, Japan.
Neuropathology. 2025 Aug;45(4):e70020. doi: 10.1111/neup.70020.
Multiplication of the α-synuclein gene (SNCA) can cause familial Parkinson's disease (PD). In the present study, we investigated the neuropathological and biochemical profiles in the central and peripheral nervous systems of an autopsy case with SNCA duplication. The patient began to show gait disturbance and resting tremors at the age of 34. The motor symptoms of the patient responded well to levodopa therapy. However, the condition progressed to Hoehn and Yahr stage V at age 44, and the patient died of toxic shock syndrome at age 46. Post-mortem neuropathological examination revealed some common features of SNCA duplication, such as prominent neuronal loss in the substantia nigra and locus coeruleus, and widespread Lewy pathology from the brainstem to the neocortex. Marked Lewy neurites were also observed in the cornu Ammonis 2/3 region of the hippocampus; however, without apparent neuronal loss. Large Lewy bodies were frequently observed in the tuberomammillary nucleus of the hypothalamus. Additionally, Lewy pathology was frequently visible in the peripheral nervous system, including the sympathetic and dorsal root ganglia. Western blotting revealed bands, and immunoelectron microscopy analyses showed filaments typical of Lewy body disease in the central and peripheral nervous systems. These results show that duplication of the SNCA gene facilitates the formation of Lewy bodies in the central and peripheral nervous systems. These Lewy bodies show the same biochemical profiles as sporadic Lewy body disease.
α-突触核蛋白基因（SNCA）倍增可导致家族性帕金森病（PD）。在本研究中，我们调查了1例SNCA倍增尸检病例中枢和外周神经系统的神经病理学和生化特征。该患者34岁时开始出现步态障碍和静止性震颤。患者的运动症状对左旋多巴治疗反应良好。然而，病情在44岁时进展至Hoehn和Yahr V期，患者46岁时死于中毒性休克综合征。尸检神经病理学检查揭示了SNCA倍增的一些常见特征，如黑质和蓝斑中明显的神经元丢失，以及从脑干到新皮质广泛的路易体病变。在海马的海马2/3区也观察到明显的路易神经突；然而，没有明显的神经元丢失。在下丘脑的结节乳头体核中经常观察到大型路易体。此外，路易体病变在外周神经系统中也经常可见，包括交感神经节和背根神经节。蛋白质免疫印迹法显示有条带，免疫电子显微镜分析显示中枢和外周神经系统中存在路易体病典型的细丝。这些结果表明，SNCA基因倍增促进中枢和外周神经系统中路易体的形成。这些路易体与散发性路易体病具有相同的生化特征。
