Brain TDP‐43 pathology in corticobasal degeneration: Topographical correlation with neuronal loss
Brain TDP‐43 pathology in corticobasal degeneration: Topographical correlation with neuronal loss
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皮质基底节变性中的脑 TDP-43 病理学：与神经元损失的拓扑相关性
DOI：
10.1111/nan.12786
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发表时间：
2022
影响因子：
5
通讯作者：
Kakita Akiyoshi
中科院分区：
文献类型：
--
作者：
Sainouchi Makoto;Tada Mari;Fitrah Yusran Ady;Hara Norikazu;Tanaka Kou;Idezuka Jiro;Aida Izumi;Nakajima Takashi;Miyashita Akinori;Akazawa Kohei;Ikeuchi Takeshi;Onodera Osamu;Kakita Akiyoshi
目的：在皮质基底变性（CBD）患者的大脑中发现了包含43 kDa （TDP - 43）的交互反应DNA结合蛋白的神经元和胶质包涵体，并推测这些包涵体的存在与临床表型之间可能存在相关性。然而，TDP‐43病理在CBD病理机制中的意义尚不清楚。在这里，我们研究了CBD中TDP - 43包裹体与神经元丢失之间的地形关系。方法：我们对10例CBD患者22个中枢神经系统区域的神经元胞浆包涵体（NCIs）、星形细胞包涵体（AIs）、少突胶质胞浆包涵体（GCIs）和营养不良神经突的神经元损失和TDP - 43病理进行了半定量评估。然后，评估神经元丧失的严重程度与每种类型的TDP - 43包涵量之间的相关性。我们也以类似的方式研究了tau病理学。结果9例患者有明显的stdp - 43病理。壳核和苍白球是最常受影响的区域（80%）。NCIs是最突出的形式，其数量与半数以上被检查区域的神经元丧失的严重程度显著相关。TDP - 43 nci和tau nci的数量仅在少数地区相关。与nci相比，TDP - 43 AIs和gci数量与神经元丧失严重程度相关的区域数量明显较少。结论神经元stdp‐43的改变可能参与了CBD神经元丢失的病理机制，但与tau病理关系并不密切。在CBD中，神经元胞浆中TDP - 43的聚集与神经元的损失之间存在显著的地形相关性，这表明TDP - 43蛋白畸变可能与CBD中神经元的变性有关。神经元中TDP - 43的负荷与tau的负荷之间没有密切的相关性。
AimsNeuronal and glial inclusions comprising transactive response DNA‐binding protein of 43 kDa (TDP‐43) have been identified in the brains of patients with corticobasal degeneration (CBD), and a possible correlation between the presence of these inclusions and clinical phenotypes has been speculated. However, the significance of TDP‐43 pathology in the pathomechanism of CBD has remained unclear. Here, we investigated the topographical relationship between TDP‐43 inclusions and neuronal loss in CBD.MethodsWe estimated semi‐quantitatively neuronal loss and TDP‐43 pathology in the form of neuronal cytoplasmic inclusions (NCIs), astrocytic inclusions (AIs), oligodendroglial cytoplasmic inclusions (GCIs), and dystrophic neurites in 22 CNS regions in 10 patients with CBD. Then, the degree of correlation between the severity of neuronal loss and the quantity of each type of TDP‐43 inclusion was assessed. We also investigated tau pathology in a similar manner.ResultsTDP‐43 pathology was evident in nine patients. The putamen and globus pallidus were the regions most frequently affected (80%). NCIs were the most prominent form, and their quantity was significantly correlated with the severity of neuronal loss in more than half of the regions examined. The quantities of TDP‐43 NCIs and tau NCIs were correlated in only a few regions. The number of regions where the quantities of TDP‐43 AIs and GCIs were correlated with the severity of neuronal loss was apparently small in comparison with that of NCIs.ConclusionsTDP‐43 alterations in neurons, not closely associated with tau pathology, may be involved in the pathomechanism underlying neuronal loss in CBD.There was a significant topographical correlation between neuronal cytoplasmic aggregation of TDP‐43 and neuronal loss in CBD, suggesting that TDP‐43 protein aberration might be associated with neuronal degeneration in CBD. There was no close correlation between the burden of TDP‐43 and that of tau in neurons.
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