Updated TDP-43 in Alzheimer's disease staging scheme.
Updated TDP-43 in Alzheimer's disease staging scheme.
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DOI：
10.1007/s00401-016-1537-1
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发表时间：
2016-04
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;Tosakulwong N;Weigand SD;Petrucelli L;Liesinger AM;Petersen RC;Parisi JE;Dickson DW
在这项研究中，我们通过评估193例阿尔茨海默病患者的TDP-43在14个不同脑区（8个先前描述的加上6个新报道的）中的地形图来更新TDP-43在阿尔茨海默病分期方案中的分布，并使用条件概率来模拟TDP-43在14个脑区中的分布。我们发现，除了我们以前报道的八个原始区域外，（杏仁核、内嗅皮层、下托、海马的齿状回、枕颞皮层、下颞皮层、中额皮层和基底神经节（壳核/苍白球）），TDP-43也沉积在岛叶皮层、腹侧纹状体、基底前脑、黑质、中脑顶盖，和延髓的下橄榄核。条件概率分析产生了六个显著不同的阶段（P< 0.01），并提示TDP-43沉积开始于杏仁核（第1期），然后移到内嗅皮层和下托（第2期），再移到海马齿状回和枕颞叶皮层（第3期），然后移到岛叶皮层、腹侧纹状体、基底前脑和颞叶下皮层（第4期），然后是黑质、下橄榄和中脑顶盖（第5期），最后是基底节和中额皮质（第6期）。这种更新的分期方案上级我们以前的分期方案，根据提供的标准对100%的病例进行分类（而旧方案为94%），并且更好地解释了阿尔茨海默病的临床和成像特征，如简易精神状态检查评分和海马体积。我们讨论了更新的分期方案的相关性，以及它对神经退行性疾病中蛋白质扩散的朊病毒样假说的影响。我们还讨论了TDP-43引起的额颞叶变性是否可能是第6期的主要病理学。
In this study we update the TDP-43 in Alzheimer’s disease staging scheme by assessing the topography of TDP-43 in 193 cases of Alzheimer’s disease, in 14 different brain regions (eight previously described plus six newly reported) and use conditional probability to model the spread of TDP-43 across the 14 brain regions. We show that in addition to the eight original regions we previously reported (amygdala, entorhinal cortex, subiculum, dentate gyrus of the hippocampus, occipitotemporal cortex, inferior temporal cortex, middle frontal cortex and basal ganglia (putamen/globus pallidum)), that TDP-43 is also deposited in the insular cortex, ventral striatum, basal forebrain, substantia nigra, midbrain tectum, and the inferior olive of the medulla oblongata, in Alzheimer’s disease. The conditional probability analysis produced six significantly different stages (P< 0.01), and suggest that TDP-43 deposition begins in the amygdala (stage 1), then moves to entorhinal cortex and subiculum (stage 2), then to the dentate gyrus of the hippocampus and occipitotemporal cortex (stage 3), then insular cortex, ventral striatum, basal forebrain and inferior temporal cortex (stage 4), then substantia nigra, inferior olive and midbrain tectum (stage 5), and finally to basal ganglia and middle frontal cortex (stage 6). This updated staging scheme is superior to our previous staging scheme, classifying 100 % of the cases (versus 94% in the old scheme), based on criteria provided, and better accounts for Alzheimer’s disease clinical and imaging features, such as Mini-Mental Status Examination score and hippocampal volume. We discuss the relevance of the updated staging scheme, as well as its impact on the prion-like hypothesis of protein spread in neurodegenerative disease. We also address the issue of whether frontotemporal lobar degeneration with TDP-43 could be the primary pathology in stage 6.
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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：
11.2
作者：
Josephs KA;Whitwell JL;Tosakulwong N;Weigand SD;Murray ME;Liesinger AM;Petrucelli L;Senjem ML;Ivnik RJ;Parisi JE;Petersen RC;Dickson DW
通讯作者：
Dickson DW
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：
Kadokura, Ai;Yamazaki, Tsuneo;Okamoto, Koichi
通讯作者：
Okamoto, Koichi