Abnormal TDP-43 expression is identified in the neocortex in cases of dementia pugilistica, but is mainly confined to the limbic system when identified in high and moderate stages of Alzheimer's disease
Abnormal TDP-43 expression is identified in the neocortex in cases of dementia pugilistica, but is mainly confined to the limbic system when identified in high and moderate stages of Alzheimer's disease
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DOI：
10.1111/j.1440-1789.2009.01085.x
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发表时间：
2010-08-01
期刊：
影响因子：
2.3
通讯作者：
Al-Sarraj, Safa
中科院分区：
文献类型：
--
作者：
King, Andrew;Sweeney, Fiona;Al-Sarraj, Safa
反式反应（TAR）DNA结合蛋白TDP-43被发现是额颞叶变性伴泛素化tau阴性包涵体（FTLD-U）中的主要泛素化蛋白，因此被重新命名为FTLD-TDP。然而，TDP-43已经在阿尔茨海默病（AD）和路易体痴呆（DLB）等疾病中被检测到，但通常局限于边缘区域，而不是FTLD-TDP中更广泛的模式。以前的工作表明海马硬化和TDP-43表达之间存在一定的关系。一些AD的情况下，中，高阶段进行了检查，以确定是否TDP-43免疫组化表达的模式不同，是否有任何关系，海马硬化可以检测到。对来自手术癫痫标本的海马硬化病例进行检查，以确定海马硬化是否单独引起TDP-43表达异常。为了确定其他神经退行性疾病中的异常TDP-43表达是否与FTLD-TDP中的模式和分布相似，我们检查了来自各种神经退行性疾病的多个块。在75%的高级AD病例中，TDP-43阳性异常，而中度AD为57%。虽然异常的TDP-43阳性仅限于边缘区在中度阶段，偶尔的情况下，在高阶段显示新皮质阳性。此外，杏仁核和/或内嗅阳性出现在齿状回阳性之前。在手术或尸检病例中，TDP-43的异常表达与海马硬化程度之间没有关系。拳击员痴呆病例中TDP-43包涵体的分布模式与FTLD-TDP最相似。这就提出了一个问题，即这两种疾病之间是否存在一些共同的致病机制。
The transactive response (TAR) DNA binding protein TDP-43 has been discovered to be a major ubiquitinated protein in frontotemporal lobar degeneration with ubiquitinated tau-negative inclusions (FTLD-U), which consequently has been renamed FTLD-TDP. However, TDP-43 has since been detected in conditions such as Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) but is often confined to the limbic region rather than the more widespread pattern seen in FTLD-TDP. Previous work has suggested some relationship between hippocampal sclerosis and TDP-43 expression. A number of AD cases of both moderate and high stage were examined to determine whether the pattern of TDP-43 immunohistochemical expression differed and whether any relationship to hippocampal sclerosis could be detected. Cases of hippocampal sclerosis from surgical epilepsy specimens were examined to determine whether hippocampal sclerosis alone could cause abnormal TDP-43 expression. To establish whether abnormal TDP-43 expression in other neurodegenerative diseases resembled the pattern and distribution in FTLD-TDP we examined multiple blocks from a variety of neurodegenerative conditions. In 75% of cases of high-stage AD there was abnormal TDP-43 positivity compared to 57% of moderate-stage AD. While the abnormal TDP-43 positivity was confined to the limbic regions in the moderate stages, occasional cases in the high stages showed neocortical positivity. Also amygdala and/or entorhinal positivity appeared to precede positivity in the dentate gyrus. No relationship could be established between abnormal TDP-43 expression and degree of hippocampal sclerosis either in the surgical or autopsy cases. The pattern of distribution of TDP-43 inclusions from cases of dementia pugilistica most closely resembled that in FTLD-TDP. This raises the question as to whether there may be some shared pathogenic mechanisms between the two conditions.