Concomitant TAR-DNA-binding in Alzheimer disease and protein 43 pathology is present corticobasal degeneration but not in other tauopathies
Concomitant TAR-DNA-binding in Alzheimer disease and protein 43 pathology is present corticobasal degeneration but not in other tauopathies
复制标题
DOI：
10.1097/nen.0b013e31817713b5
复制
发表时间：
2008-06-01
影响因子：
3.2
通讯作者：
Neumann, Manuela
中科院分区：
文献类型：
--
作者：
Uryu, Kunihiro;Nakashima-Yasuda, Hanae;Neumann, Manuela
病理性 TAR-DNA 结合蛋白 43 (TDP-43) 是泛素阳性包涵体额颞叶变性 (FTLD-U) 和肌萎缩侧索硬化症中的一种疾病蛋白。我们通过免疫组织化学和生物化学研究了一系列临床上明确表征的 tau 蛋白病患者大脑中 TDP-43 病理的存在、频率和分布，包括 182 例阿尔茨海默病 (AD)、39 例皮质基底节变性、77 例进行性核上性麻痹和 12 例 Pick 病病例，并研究了这些病例中伴随 TDP-43 病理的临床影响。 TAR-DNA 结合蛋白 43 病理学在 25.8% 的 AD 病例中被发现。大约 75% 的病例仅限于齿状回和内嗅皮层；大约 25% 在额叶和颞叶皮质中表现出更广泛的 TDP-43 病理，类似于与颗粒体蛋白前体突变相关的 FTLD-U 亚型。 AD 中的 TAR-DNA 结合蛋白 43 病理学与明显较长的病程相关，但与临床表现无关（148 例诊断为 AD，34 例诊断为额颞叶变性）。进行性核上性麻痹和匹克病病例显示没有 TDP-43 包涵体，也没有 TDP-43 的生化改变。然而，在 15.4% 的皮质基底节变性病例中，存在一种独特的、主要是胶质细胞的 TDP-43 病理学，伴有星形胶质细胞斑状结构和卷曲体染色；这与类似于 FTLD-U 中的生化 TDP-43 变化有关。这些发现进一步了解了 TDP-43 病理学在 FTLD-U 和肌萎缩侧索硬化症以外的疾病中的负担和临床意义。
Pathologic TAR-DNA-binding protein 43 (TDP-43) is a disease protein in frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) and amyotrophic lateral sclerosis. We studied the presence, frequency, and distribution of TDP-43 pathology by immunohistochemistry and biochemistry in a series of clinically well-characterized tauopathy patient brains, including 182 Alzheimer disease (AD), 39 corticobasal degeneration, 77 progressive supranuclear palsy, and 12 Pick disease cases and investigated the clinical impact of concomitant TDP-43 pathology in these cases. TAR-DNA-binding protein 43 pathology was found in 25.8% of AD cases. It was restricted to the dentate gyrus and entorhinal cortex in approximately 75% of cases; approximately 25% showed more widespread TDP-43 pathology in frontal and temporal cortices, resembling the FTLD-U subtype associated with progranulin mutations. TAR-DNA-binding protein 43 pathology in AD was associated with significantly longer disease duration, but there was no association with the clinical presentation (148 cases diagnosed as AD and 34 cases diagnosed as frontotemporal lobar degeneration). Progressive supranuclear palsy and Pick disease cases showed no TDP-43 inclusions and no biochemical alterations of TDP-43. There was, however, a unique, predominantly glial TDP-43 pathology with staining of astrocytic plaque-like structures and coiled bodies in 15.4% of corticobasal degeneration cases; this was associated with biochemical TDP-43 changes similar to those in FTLD-U. These findings provide further insight into the burden and clinical significance of TDP-43 pathology in disorders other than FTLD-U and amyotrophic lateral sclerosis.