α-Synuclein accumulates in Purkinje cells in Lewy body disease but not in multiple system atrophy
α-Synuclein accumulates in Purkinje cells in Lewy body disease but not in multiple system atrophy
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DOI：
10.1093/jnen/62.8.812
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发表时间：
2003-08-01
影响因子：
3.2
通讯作者：
Wakabayashi, K
中科院分区：
文献类型：
--
作者：
Mori, F;Piao, YS;Wakabayashi, K
α-突触核蛋白在帕金森病(PD)、路易体痴呆(DLB)和多系统萎缩(MSA)的发病机制中起着重要作用，形成了一个新的疾病概念--α-突触核苷酸病。小脑变性伴浦基尼细胞耗竭出现在大多数MSA病例中。相反，小脑病理在帕金森病和弥漫性淋巴细胞性脑病中都没有明确的表现。最近使用抗α-突触核蛋白抗体的免疫组织化学研究表明，LB型变性在PD和DLB中比以前认识的更普遍。为了确定小脑浦肯野细胞是否可能参与α-突触核蛋白的病理变化，我们用α-突触核蛋白特异性抗体对帕金森病患者(n=10)、DLB患者(n=7)、MSA患者(n=10)、阿尔茨海默病和其他疾病患者(n=9)和年龄匹配的对照组(n=10)的小脑进行了免疫组织化学检查。帕金野细胞胞体未见α-突触核蛋白异常积聚，但所有PD和DLB患者的小脑白质均可见大量α-突触核蛋白阳性圆形包涵体。免疫组织化学和超微结构检查显示，这些包涵体大部分位于浦肯野细胞轴突内，由颗粒丝状结构组成。在MSA、tauopathy或对照组中没有观察到这样的包涵体。这些发现表明，浦肯野细胞也是帕金森病和DLB的α-突触核蛋白病理的受害者，但在MSA中不是。
alpha-Synuclein has an important role in the pathogenesis of Parkinson disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), comprising a new disease concept, that of alpha-synucleinopathies. Cerebellar degeneration with Purkinie cell depletion is present in the majority of MSA cases. By contrast, cerebellar pathology has not been demonstrated unequivocally in either PD or DLB. Recent immunohistochemical studies using anti-alpha-synuclein antibodies have shown that LB-type degeneration in PD and DLB is more widespread than previously recognized. To determine whether cerebellar Purkinje cells might be involved in alpha-synuclein pathology, we carried out immunohistochemical examinations of the cerebella of patients with PD (n = 10), DLB (n = 7), MSA (n = 10), Alzheimer disease and other tauopathies (n = 9), and age-matched control subjects (n = 10), using antibodies specific for alpha-synuclein. Although no abnormal accumulation of alpha-synuclein was noted in the Purkinje cell somata, numerous alpha-synuclein-positive, round inclusions were found in the cerebellar white matter in all the patients with PD and DLB. Immunohistochemical and ultrastructural examinations revealed that the majority of these inclusions was located in the Purkinje cell axons and consisted of granulo-filamentous structures. No such inclusions were observed in MSA, tauopathies, or controls. These findings indicate that Purkinje cells are also the victims of alpha-synuclein pathology in PD and DLB, but not in MSA.