Expansion of the classification of FTLD-TDP: distinct pathology associated with rapidly progressive frontotemporal degeneration.
Expansion of the classification of FTLD-TDP: distinct pathology associated with rapidly progressive frontotemporal degeneration.
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DOI：
10.1007/s00401-017-1679-9
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发表时间：
2017-07
影响因子：
12.7
通讯作者：
Trojanowski JQ
中科院分区：
文献类型：
--
作者：
Lee EB;Porta S;Michael Baer G;Xu Y;Suh E;Kwong LK;Elman L;Grossman M;Lee VM;Irwin DJ;Van Deerlin VM;Trojanowski JQ
额颞叶变性伴TDP-43包涵体（FTLD-TDP）通常可分为TDP-43病理学的四种不同组织病理学模式之一，A型至D型。这种组织病理学分类的优势在于FTLD-TDP亚型与疾病的各种临床和遗传特征之间的关联。在此确定了7例FTLD-TDP病例，根据现有的病理标准难以分类。这些病例共同的独特特征包括TDP-43聚集在广泛的神经解剖分布，包括颗粒丝状神经元包涵体，丰富的颗粒和少突胶质细胞包涵体。TDP-43聚集体被磷酸化，并与正常核TDP-43蛋白（核清除）的损失有关，但对泛素呈阴性。生化分析证实了不溶性和磷酸化TDP-43的存在，也揭示了TDP-43 C-末端片段相对于其他FTLD-TDP亚型的独特模式。最后，这些病例均与非常快速的临床病程相关，在发病后约3年内死亡。我们认为这些病例可能代表了FTLD-TDP的一种独特的临床病理亚型，我们暂时称之为“E型”。TDP-43聚集体的不成熟外观、广泛分布、均匀的生化特征和快速的临床过程突出了FTLD-TDP内的临床和病理变异性，并提出了E型神经病理学是TDP-43蛋白病的特别强毒株的后遗症的可能性。
Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) can typically be categorized into one of four distinct histopathologic patterns of TDP-43 pathology, types A to D. The strength of this histopathologic classification lies in the association between FTLD-TDP subtypes and various clinical and genetic features of disease. Seven cases of FTLD-TDP were identified here which were difficult to classify based on existing pathologic criteria. Distinct features common to these cases included TDP-43 aggregates over a wide neuroanatomic distribution comprised of granulofilamentous neuronal inclusions, abundant grains, and oligodendroglial inclusions. TDP-43 aggregates were phosphorylated and associated with loss of normal nuclear TDP-43 protein (nuclear clearance) but were negative for ubiquitin. Biochemical analysis confirmed the presence of insoluble and phosphorylated TDP-43 and also revealed a distinct pattern of TDP-43 C-terminal fragments relative to other FTLD-TDP subtypes. Finally, these cases were uniformly associated with a very rapid clinical course culminating in death within ~3 years of disease onset. We suggest that these cases may represent a unique clinicopathologic subtype of FTLD-TDP which we provisionally call “type E.” The immature appearance of TDP-43 aggregates, widespread distribution, uniform biochemical profile and rapid clinical course highlights the clinical and pathologic variability within FTLD-TDP, and raises the possibility that type E neuropathology is the sequelae of a particularly virulent strain of TDP-43 proteinopathy.
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影响因子：
16.2
作者：
Giasson, BI;Duda, JE;Lee, VMY
通讯作者：
Lee, VMY
影响因子：
9.9
作者：
Rohrer, J. D.;Guerreiro, R.;Rossor, M. N.
通讯作者：
Rossor, M. N.
影响因子：
--
作者：
Geser, Felix;Martinez-Lage, Maria;Trojanowski, John Q.
通讯作者：
Trojanowski, John Q.
影响因子：
6
作者：
Cairns, Nigel J.;Neumann, Manuela;Mackenzie, Ian R. A.
通讯作者：
Mackenzie, Ian R. A.
影响因子：
7.1
作者：
Kwong, Linda K.;Irwin, David J.;Lee, Virginia M. Y.
通讯作者：
Lee, Virginia M. Y.