Acta Neuropathol Commun. 2015 Apr 1;3:15. doi: 10.1186/s40478-015-0195-1.
Frontotemporal lobar degeneration (FTLD) is one of the leading causes of dementia after Alzheimer's disease. A high-ranking candidate to become a diagnostic marker for a major pathological subtype of FTLD is the transactive response DNA binding protein of 43 kDa (TDP-43). The main objective is to elucidate which antibodies are specific for pathological TDP-43, with special interest in its modified isoforms. Indeed, TDP-43 has been shown to be hyperphosphorylated and truncated in disease. A secondary objective is to review existing immunoassays that quantify TDP-43 in biofluids. A systematic review of literature was performed by searching PubMed and Web of Science using predefined keywords. Of considered research papers the methods section was reviewed to select publications that enabled us to answer our learning objective. After quality assessment, antibody characteristics and related outcomes were extracted. We identified a series of well-characterized antibodies based on a scoring system that assessed the ability of each antibody to detect TDP-43 pathology. A selection of 29 unique antibodies was made comprising 10 high-ranking antibodies which were reported multiple times to detect TDP-43 pathology in both immunostaining and immunoblotting experiments and 19 additional antibodies which detected TDP-43 pathology but were only scored once. This systematic review provides an overview of antibodies that are reported to detect pathological TDP-43. These antibodies can be used in future studies of TDP-43 proteinopathies. Additionally, selected antibodies hold the potential to be used in the development of novel immunoassays for the quantification of TDP-43 in biofluids, as a possible biomarker for FTLD-TDP.
额颞叶痴呆（FTLD）是继阿尔茨海默病之后导致痴呆的主要原因之一。转激活反应 DNA 结合蛋白 43kDa（TDP-43）是 FTLD 主要病理亚型的一种有前途的诊断标志物候选物。主要目标是阐明哪些抗体是针对病理性 TDP-43 的特异性抗体，特别关注其修饰异构体。事实上，TDP-43 在疾病中已被证明发生过度磷酸化和截断。次要目标是综述现有的用于定量生物体液中 TDP-43 的免疫测定法。通过使用预定义的关键字在 PubMed 和 Web of Science 上进行文献系统综述。在考虑的研究论文中，对方法部分进行了审查，以选择能够回答我们学习目标的出版物。经过质量评估，提取了抗体特性和相关结果。我们根据评估每个抗体检测 TDP-43 病理学能力的评分系统，确定了一系列经过良好特征描述的抗体。选择了 29 种独特的抗体，其中包括 10 种高排名抗体，这些抗体在免疫染色和免疫印迹实验中多次报道可检测 TDP-43 病理学，以及 19 种额外的抗体可检测 TDP-43 病理学，但仅评分一次。本系统综述提供了已报道可检测病理性 TDP-43 的抗体概述。这些抗体可用于未来 TDP-43 蛋白病的研究。此外，选定的抗体有可能被用于开发新型免疫测定法，以定量生物体液中的 TDP-43，作为 FTLD-TDP 的潜在生物标志物。
