Nakashima-Yasuda Hanae, Uryu Kunihiro, Robinson John, Xie Sharon X, Hurtig Howard, Duda John E, Arnold Steven E, Siderowf Andrew, Grossman Murray, Leverenz James B, Woltjer Randy, Lopez Oscar L, Hamilton Ronald, Tsuang Debby W, Galasko Douglas, Masliah Eliezer, Kaye Jeffrey, Clark Christopher M, Montine Thomas J, Lee Virginia M-Y, Trojanowski John Q
Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, HUP/Maloney 3rd Floor, Philadelphia, PA 19104-4283, USA.
Acta Neuropathol. 2007 Sep;114(3):221-9. doi: 10.1007/s00401-007-0261-2. Epub 2007 Jul 25.
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 no (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.
在此，我们研究了在额颞叶变性以及伴有或不伴有运动神经元病及肌萎缩侧索硬化的泛素包涵体疾病中的致病蛋白——Tar-DNA结合蛋白43（TDP-43），是否也会在路易体（LB）疾病中形成包涵体，这些疾病包括不伴有或伴有痴呆的帕金森病（PD）（帕金森病痴呆，PDD），以及仅患有路易体痴呆（DLB）或合并阿尔茨海默病（AD）的情况。对临床特征明确且经病理证实的DLB + AD、PD和PDD病例进行TDP-43免疫组化分析，结果显示TDP-43病理改变在以下病例中的占比为：DLB + AD = 25/80（31.3%）；PD = 5/69（7.2%）；PDD = 4/21（19%），而DLB和正常对照分别有0/10（0%）和1/33（3%）的病例出现TDP-43病理改变。疾病组与正常脑组之间（P < 0.001）以及痴呆组与非痴呆组之间（P < 0.001）TDP-43病变患病率存在显著差异。统计分析显示，这些疾病中TDP-43病变与若干临床和病理参数之间呈正相关，提示TDP-43病理改变可能在LB疾病中具有共病效应。本研究通过将TDP-43病变与LB疾病的神经退行性变机制相关联，扩展了TDP-43蛋白病的概念。
