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从tau蛋白病角度看路易体痴呆

Dementia with Lewy bodies from the perspective of tauopathy.

作者信息

Iseki Eizo, Togo Takashi, Suzuki Kyoko, Katsuse Omi, Marui Wami, de Silva Rohan, Lees Andrews, Yamamoto Takayuki, Kosaka Kenji

机构信息

Department of Psychiatry, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Japan.

出版信息

Acta Neuropathol. 2003 Mar;105(3):265-70. doi: 10.1007/s00401-002-0644-3. Epub 2002 Nov 22.

Abstract

We immunohistochemically investigated the prevalence and pattern of phosphorylated tau accumulation in neurons and glia in 46 cases of dementia with Lewy bodies (DLB). Tau-positive neurons composed of neurofibrillary tangles (NFT) and pretangle neurons were found in the hippocampal area in all 46 cases, although the ratio of pretangle neurons in tau-positive neurons was higher in the cases showing low NFT stages. Tau-positive astrocytes were found in the periventricular area in 18 of 46 cases, and partly represented argyrophilic thorn-shaped astrocytes. In contrast, tau-positive oligodendroglia were found in the subcortical white matter in 9 of 46 cases, and represented argyrophilic coiled bodies. Tau-positive argyrophilic grains were found in the hippocampal area in the same cases as those with coiled bodies. The 9 cases with tau-positive coiled bodies and grains were included in the 18 cases with tau-positive astrocytes, and showed larger proportions in the low NFT stages than the 46 cases with tau-positive neurons. Tau-positive neurons were positive both to anti-three-repeat (3R) and -4R tau-specific antibodies, while tau-positive astrocytes, coiled bodies and grains were predominantly positive to anti-4R tau-specific antibody. These tau-positive structures were negative to anti-alpha-synuclein antibody. These findings suggest that the tau accumulation in DLB represents both tau-positive neurons with all six tau isoforms and tau-positive astrocytes, coiled bodies and grains with the 4R tau isoform, and that the different cytoskeletal abnormalities form a link between some neurodegenerative dementing disorders including DLB.

摘要

我们采用免疫组化方法研究了46例路易体痴呆(DLB)患者神经元和胶质细胞中磷酸化tau蛋白积累的发生率及模式。在所有46例患者的海马区均发现了由神经原纤维缠结(NFT)和缠结前神经元组成的tau阳性神经元,不过在NFT分期较低的病例中,缠结前神经元在tau阳性神经元中的比例更高。46例中有18例在脑室周围区域发现了tau阳性星形胶质细胞,部分表现为嗜银刺状星形胶质细胞。相比之下,46例中有9例在皮质下白质中发现了tau阳性少突胶质细胞,表现为嗜银卷曲小体。在与出现卷曲小体的相同病例的海马区发现了tau阳性嗜银颗粒。9例出现tau阳性卷曲小体和颗粒的病例包含在18例出现tau阳性星形胶质细胞的病例中,且在低NFT分期中的比例高于46例出现tau阳性神经元的病例。tau阳性神经元对抗三重复(3R)和抗4R tau特异性抗体均呈阳性,而tau阳性星形胶质细胞、卷曲小体和颗粒主要对抗4R tau特异性抗体呈阳性。这些tau阳性结构对抗α-突触核蛋白抗体呈阴性。这些发现表明,DLB中的tau蛋白积累既包括具有所有六种tau异构体的tau阳性神经元,也包括具有4R tau异构体的tau阳性星形胶质细胞、卷曲小体和颗粒,并且不同的细胞骨架异常在包括DLB在内的一些神经退行性痴呆疾病之间形成了联系。

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