Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases
Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases
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DOI：
10.1007/s00401-007-0261-2
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发表时间：
2007-09-01
影响因子：
12.7
通讯作者：
Trojanowski, John Q.
中科院分区：
文献类型：
--
作者：
Nakashima-Yasuda, Hanae;Uryu, Kunihiro;Trojanowski, John Q.
在这里，我们研究了TAR-DNA结合蛋白-43（TDP-43），即在有或没有运动神经元疾病以及肌萎缩侧索硬化的额颞叶变性和泛素包涵体中的疾病蛋白，是否也在路易体（LB）疾病包括帕金森病（PD）中形成包涵体，以及单独的或与阿尔茨海默病（AD）相关的伴有LB的痴呆（DLB）。在临床上充分表征和病理学证实的DLB + AD、PD和PDD病例中的TDP-43的免疫组织化学分析证实了以下病例百分比中的TDP-43病理学：DLB和正常对照分别显示Do（0/10，0%）和1例（1/33，3%）呈现TDP-43病理。TDP-43病变的患病率在疾病与正常大脑之间（P < 0.001）以及痴呆与非痴呆大脑之间（P < 0.001）存在显著差异。统计学分析揭示了TDP-43病变与这些疾病中的几个临床和病理学参数之间的正相关性，表明TDP-43病理学可能在LB疾病中具有共病效应。本研究通过将TDP-43病变与LB疾病的神经变性机制联系起来，扩展了TDP-43蛋白病的概念。
Here, we investigated if TAR-DNA-binding protein-43 (TDP-43), the disease protein-in frontotemporal lobar degeneration and ubiquitin inclusions with or without motor neuron disease as well as amyotrophic lateral sclerosis, also formed inclusions in Lewy body (LB) disorders including Parkinson's disease (PD) without or with dementia (PDD), and dementia with LBs (DLB) alone or in association with Alzheimer's disease (AD). Immunohistochemical analyses of TDP-43 in clinically well characterized and pathologically confirmed cases of DLB + AD, PD and PDD demonstrated TDP-43 pathology in the following percentage of cases: DLB + AD = 25/80 (31.3%); PD = 5/69 (7.2%); PDD 4/21 (19%), while DLB and normal controls exhibited Do (0/10, 0%) and one cases (1/33, 3%) presenting TDP-43 pathology, respectively. Significant differences in the prevalence of TDP-43 lesions were noted between disease versus normal brains (P < 0.001) as well as demented versus non-demented brains (P < 0.001). Statistical analyses revealed a positive relationship between TDP-43 lesions and several clinical and pathological parameters in these disorders suggesting the TDP-43 pathology may have co-morbid effects in LB diseases. This study expands the concept of TDP-43 proteinopathies by implicating TDP-43 lesions in mechanisms of neurodegeneration in LB disorders.