Staging TDP-43 pathology in Alzheimer's disease.
Staging TDP-43 pathology in Alzheimer's disease.
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DOI：
10.1007/s00401-013-1211-9
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发表时间：
2014-03
影响因子：
12.7
通讯作者：
Dickson DW
中科院分区：
文献类型：
--
作者：
Josephs KA;Murray ME;Whitwell JL;Parisi JE;Petrucelli L;Jack CR;Petersen RC;Dickson DW
TDP-43免疫反应出现在19-57%的阿尔茨海默病(AD)病例中。阿尔茨海默病患者TDP-43的两种沉积模式已被描述为累及海马体(边缘)或海马体和新皮质(弥漫性)，尽管观察到局灶性杏仁核受累。在195例伴有TDP-43的AD患者中，我们研究了局部TDP-43的免疫反应性，旨在建立一种TDP-43在AD分期中的应用方案。观察TDP-43在杏仁核、内嗅皮质、下丘脑、海马齿状回、枕颞叶、额叶下皮质和基底节的免疫反应。临床、神经影像、遗传和病理特征被分阶段进行评估。可分为5个阶段：I期仅杏仁核内TDP-43稀疏(17%)；II期TDP-43呈中度频发，累及内嗅和下丘(25%)；III期进一步累及齿状回和枕颞叶(31%)；IV期进一步累及颞叶下部(20%)；V期累及额叶和基底节(7%)。认知和内侧颞叶体积在所有阶段都不同，不同阶段的进展与认知恶化和内侧颞叶体积丧失相关。与147例没有TDP-43的AD患者相比，只有波士顿命名测验在I期显示异常。研究结果表明，TDP-43在AD中的沉积是以刻板的方式进行的，可以分为五个不同的地形学阶段，这与临床和神经影像特征的相关性得到了支持。鉴于这些发现，我们建议从杏仁核开始对AD患者进行TDP-43序贯区域筛查。
TDP-43 immunoreactivity occurs in 19–57% of Alzheimer’s disease (AD) cases. Two patterns of TDP-43 deposition in AD have been described involving hippocampus (Limbic) or hippocampus and neocortex (Diffuse), although focal amygdala involvement has been observed. In 195 AD cases with TDP-43, we investigated regional TDP-43 immunoreactivity with the aim of developing a TDP-43 in AD staging scheme. TDP-43 immunoreactivity was assessed in amygdala, entorhinal cortex, subiculum, hippocampal dentate gyrus, occipitotemporal, inferior temporal and frontal cortices, and basal ganglia. Clinical, neuroimaging, genetic and pathological characteristics were assessed across stages. Five stages were identified: stage I showed scant-sparse TDP-43 in the amygdala only (17%); stage II showed moderate-frequent amygdala TDP-43 with spread into entorhinal and subiculum (25%); stage III showed further spread into dentate gyrus and occipitotemporal cortex (31%); stage IV showed further spread into inferior temporal cortex (20%); and stage V showed involvement of frontal cortex and basal ganglia (7%). Cognition and medial temporal volumes differed across all stages and progression across stages correlated with worsening cognition and medial temporal volume loss. Compared to 147 AD patients without TDP-43, only the Boston Naming Test showed abnormalities in stage I. The findings demonstrate that TDP-43 deposition in AD progresses in a stereotypic manner that can be divided into five distinct topographic stages which are supported by correlations with clinical and neuroimaging features. Given these findings, we recommend sequential regional TDP-43 screening in AD beginning with the amygdala.
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影响因子：
12.7
作者：
Bigio EH;Mishra M;Hatanpaa KJ;White CL 3rd;Johnson N;Rademaker A;Weitner BB;Deng HX;Dubner SD;Weintraub S;Mesulam M
通讯作者：
Mesulam M
影响因子：
14.5
作者：
Nelson, Peter T.;Schmitt, Frederick A.;Kryscio, Richard J.
通讯作者：
Kryscio, Richard J.
影响因子：
12.7
作者：
Josephs, Keith A.;Stroh, Alex;Dickson, Dennis W.
通讯作者：
Dickson, Dennis W.
影响因子：
12.7
作者：
Arai, Tetsuaki;Mackenzie, Ian R. A.;Akiyama, Haruhiko
通讯作者：
Akiyama, Haruhiko
影响因子：
2.3
作者：
King, Andrew;Sweeney, Fiona;Al-Sarraj, Safa
通讯作者：
Al-Sarraj, Safa