Iseki Eizo, Togo Takashi, Suzuki Kyoko, Katsuse Omi, Marui Wami, de Silva Rohan, Lees Andrews, Yamamoto Takayuki, Kosaka Kenji
Department of Psychiatry, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Japan.
Acta Neuropathol. 2003 Mar;105(3):265-70. doi: 10.1007/s00401-002-0644-3. Epub 2002 Nov 22.
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.
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。