Concurrence of TDP-43, tau and α-synuclein pathology in brains of Alzheimer's disease and dementia with Lewy bodies
Concurrence of TDP-43, tau and α-synuclein pathology in brains of Alzheimer's disease and dementia with Lewy bodies
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DOI：
10.1016/j.brainres.2007.09.048
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发表时间：
2007-12-12
期刊：
影响因子：
2.9
通讯作者：
Arai, Heii
中科院分区：
文献类型：
--
作者：
Higashi, Shinji;Iseki, Eizo;Arai, Heii
在肌萎缩性侧索硬化症伴泛素阳性包络体（FTLD-U）的额颞叶变性患者的大脑中，已鉴定出ar - dna结合蛋白43 （TDP-43）是泛素阳性包络体的主要组成蛋白。为了获得TDP-43病理在神经退行性疾病中的确切患病率，我们使用免疫组织化学分析检查了tau病和突触病以及FTLD-U患者的大脑。因此，在阿尔茨海默病（AD）和路易体痴呆（DLB）患者的大脑中，除了FTLD-U外，神经元和少突胶质细胞内也发现了tdp -43阳性包涵体，但在帕金森病、皮克病、进行性核上性麻痹、皮质基底变性或FTDP-17患者的大脑中没有发现tdp -43阳性包涵体。杏仁核。易受tau或α -突触核蛋白病理影响的海马中，AD和DLB病例的TDP-43病理比FTLD-U病例更严重。相比之下，在FTLD-U中易受TDP-43病理影响的额叶皮质和基底神经节中，AD和DLB病例未观察到TDP-43病理。因此，AD和DLB病例病理中TDP-43的神经解剖分布与FTLD-U病例明显不同。此外，tdp -43阳性包涵体的一个子集与神经原纤维缠结（nft）或利维体（LBs）在同一神经元中共存。通过双免疫荧光标记分析，TDP-43几乎没有与tau蛋白重叠，而TDP-43与α -突触核蛋白部分重叠，提示nft和LBs本身都没有表现出TDP-43的免疫反应性，本研究中发现的TDP-43病理可能与AD和LB病理有一定的关系。这项研究将提供更深入的了解导致神经退行性疾病的各种致病途径。BRAIN RESEARCH (c) 2007 Elsevier B.V.版权所有
TAR-DNA-binding protein 43 (TDP-43) has been identified as a major component protein of ubiquitin-positive inclusions in brains from patients with frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) and amyotrophic lateral sclerosis. To obtain the precise prevalence of TDP-43 pathology in neurodegenerative disorders, we examined brains from patients with tauopathies and symicleinopathies as well as FTLD-U using immunohistochemical analysis. Consequently, TDP-43-positive inclusions within neurons and oligodendroglia were found in brains from patients with Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) in addition to FTLD-U, but not with Parkinson's disease, Pick's disease, progressive supranuclear palsy, corticobasal degeneration or FTDP-17. The amygdala. and hippocampus that were vulnerable to tau or alpha-synuclein pathology demonstrated more severe TDP-43 pathology in AD and DLB cases than in FTLD-U cases. In contrast, in the frontal cortex and basal ganglia that were vulnerable to TDP-43 pathology in FTLD-U, TDP-43 pathology was not observed in AD and DLB cases. Thus, the neuroanatomical distribution of TDP-43 pathology in AD and DLB cases was obviously different from that in FTLD-U cases. Furthermore, a subset of TDP-43-positive inclusions co-existed with neurofibrillary tangles (NFTs) or Levvy bodies (LBs) in the same neurons. Upon double -immunofluorescent labeling analysis, TDP-43 was hardly superimposed with tau, while TDP-43 was partially superimposed with alpha-synuclein, suggesting that neither NFTs nor LBs themselves show TDP-43 immunoreactivity and that TDP-43 pathology found in this study may be related in some way to AD and LB pathology. This study will provide a more in-depth understanding of the various pathogenic pathways leading to neurodegenerative disorders. BRAIN RESEARCH (c) 2007 Elsevier B.V. All rights reserved.