TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease
TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease
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DOI：
10.1002/ana.21154
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发表时间：
2007-05-01
影响因子：
11.2
通讯作者：
Dickson, Dennis W.
中科院分区：
文献类型：
--
作者：
Amador-Ortiz, Catalina;Lin, Wen-Lang;Dickson, Dennis W.
目的：本研究旨在通过免疫组化检测TAR DNA结合蛋白43（TDP-43）（FTLD-U的一种假定标记物），确定海马硬化（HpScl）和阿尔茨海默病（AD）患者中伴有泛素化包涵体的额颞叶变性（FTLD-U）的发生率。首先，21例HpScl与各种其他病理过程和74例AD患者进行了筛选FTLD-U与TDP-43免疫组化。对另外93例AD病例进行了确认研究。TDP-43抗体的特异性进行了评估，采用双免疫标记共聚焦显微镜，免疫电镜，和biochemical.Results：TDP-43免疫反应性检测在71%的Hp Scl和23%的AD病例。AD病例的TDP-43和磷酸化tau双重免疫染色显示，TDP-43免疫反应性包涵体通常与神经元缠结不同。在超微结构水平，TDP-43的免疫反应性在AD与颗粒状和丝状的胞质物质，只是偶尔与tau蛋白丝。AD病例的蛋白质印迹显示了一条带，迁移在一个更高的分子量比正常的TDP-43，不存在于AD病例没有TDP-43 immunoreactivity.Interpretation：这些结果表明，多达20%的AD病例和超过70%的HpScl病例有病理学相似的FTLD-U中发现的。这是否代表伴随的FTLD-U或类似于AD中α-突触核蛋白和tau的共定位，反映了异常蛋白构象异构体共沉积的倾向，仍有待确定。
Objective: This study aimed to determine the frequency of frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U) in the setting of hippocampal sclerosis (HpScl) and Alzheimer's disease (AD) using immunohistochemistry for TAR DNA binding protein 43 (TDP-43), a putative marker for FTLD-U.Methods: Initially, 21 cases of HpScl associated with a variety of other pathological processes and 74 cases of AD were screened for FTLD-U with TDP-43 immunohistochemistry. A confirmation study was performed on 93 additional AD cases. Specificity of TDP-43 antibodies was assessed using double-immunolabeling confocal microscopy, immunoelectron microscopy, and biochemistry.Results: TDP-43 immunoreactivity was detected in 71% of HpScl and 23% of AD cases. Double immunostaining of AD cases for TDP-43 and phospho-tau showed that the TDP-43-immunoreactive inclusions were usually distinct from neurofibrillary tangles. At the ultrastructural level, TDP-43 immunoreactivity in AD was associated with granular and filamentous cytosolic material and only occasionally associated with tau filaments. Western blots of AD cases showed a band that migrated at a higher molecular weight than normal TDP-43 that was not present in AD cases without TDP-43 immunoreactivity.Interpretation: These results suggest that as many as 20% of AD cases and more than 70% of HpScl cases have pathology similar to that found in FTLD-U. Whether this represents concomitant FTLD-U or is analogous to colocalization of alpha-synuclein and tau in AD, reflecting a propensity for codeposition of abnormal protein conformers, remains to be determined.