Clusterin/apolipoprotein J is associated with cortical Lewy bodies:: immunohistochemical study in cases with α-synucleinopathies

Clusterin/apolipoprotein J is associated with cortical Lewy bodies:: immunohistochemical study in cases with α-synucleinopathies
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DOI:
10.1007/s00401-002-0546-4
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发表时间:
2002-09-01
影响因子:
12.7
通讯作者:
Iwaki, T
Iwaki, T
中科院分区:
医学1区
文献类型:
--
作者:
Sasaki, K;Doh-ura, K;Iwaki, T

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使用免疫组织化学方法标记多种抗原,研究了帕金森病 (PD)、路易体痴呆 (DLB) 和多系统萎缩 (MSA) 等“α-突触核蛋白病”病例中的凝聚蛋白/载脂蛋白 J 蛋白表达。 DLB 病例中约 50% 的皮质路易体对凝聚素具有免疫反应性,而 PD 和 DLB 患者的脑干路易体很少与凝聚素相关。在 MSA 病例中,约 10% 的神经胶质细胞质内含物 (GCI) 中的簇蛋白也呈免疫阳性。在这些小体或内含物中,簇蛋白与α-突触核蛋白的共定位与α-突触核蛋白的免疫染色模式明显相关。聚集蛋白的亚细胞定位几乎与皮层路易体中α-突触核蛋白的同质免疫反应完全重叠;然而,在脑干路易体的光环或环状结构中未检测到簇蛋白免疫反应性。此外,一些对簇蛋白具有强烈免疫反应性的路易体仅显示出对α-突触核蛋白的微弱信号。这些结果表明,聚集蛋白可能通过先前提出的聚集蛋白的分子伴侣特性来改变α-突触核蛋白阳性包涵体(例如路易体和 GCI)的形成。
Clusterin/apolipoprotein J protein expression in cases with "alpha-synucleinopathies", such as Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA), was investigated using an immunohistochemical method for the labeling of multiple antigens. About 50% of the cortical Lewy bodies in the cases with DLB were immunoreactive for clusterin, whereas brain-stem Lewy bodies in PD and DLB were rarely associated with clusterin. Clusterin was also immunopositive in around 10% of the glial cytoplasmic inclusions (GCIs) in the cases with MSA. Colocalization of clusterin with alpha-synuclein in such bodies or inclusions was clearly correlated with the immunostaining pattern of alpha-synuclein. Subcellular localization of clusterin was almost completely overlapped with the homogeneous immunoreaction of alpha-synuclein in the cortical Lewy bodies; however, clusterin immunoreactivity was not detected in the halo or ring-like structures of the brain-stem Lewy bodies. Furthermore, some Lewy bodies with intense immunoreactivity for clusterin showed only a weak signal for alpha-synuclein. These results suggest that clusterin may modify the formation of alpha-synuclein-positive inclusion bodies such as Lewy bodies and GCIs, through a previously proposed chaperone property of clusterin.