Clinical and Pathological Continuum of Multisystem TDP-43 Proteinopathies
Clinical and Pathological Continuum of Multisystem TDP-43 Proteinopathies
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DOI：
10.1001/archneurol.2008.558
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发表时间：
2009-02-01
影响因子：
--
通讯作者：
Trojanowski, John Q.
中科院分区：
文献类型：
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作者：
Geser, Felix;Martinez-Lage, Maria;Trojanowski, John Q.
目的：确定临床和尸检确诊为伴有或不伴有运动神经元疾病的额颞叶变性以及伴有和不伴有认知障碍的肌萎缩侧索硬化症患者的中枢神经系统中分子量为 43 kDa (TDP-43) 病理学反式激活反应的程度。 设计：免疫组织化学整体的表现 中枢神经系统扫描病理 TDP-43 证据和回顾性临床病历审查。地点：学术医疗中心。参与者：我们纳入了 64 名经临床和病理证实的额颞叶变性患者，伴有泛素化包涵体，伴或不伴运动神经元疾病和肌萎缩侧索硬化症，伴或不伴认知障碍。主要结果指标：神经元和神经胶质细胞 TDP-43 病理学结果：我们在整个神经轴的所有疾病组中发现了神经元和神经胶质 TDP-43 病理学的证据，尽管 TDP-43 病变的频率、形态和分布存在差异。此外，主要临床表现（例如认知障碍、运动神经元体征、锥体外系症状、神经精神特征）通过TDP-43病理学的主要分布和负担来反映。 结论：这些发现强烈提示肌萎缩侧索硬化症、额颞叶变性伴肌萎缩侧索硬化症或运动障碍 神经元疾病和额颞叶变性伴泛素化包涵体是多系统 TDP-43 蛋白病的不同表现，与类似的神经变性机制相关。
Objective: To determine the extent of transactivation response DNA-binding protein with a molecular weight of 43 kDa (TDP-43) pathology in the central nervous system of patients with clinically and autopsy-confirmed diagnoses of frontotemporal lobar degeneration with and without motor neuron disease and amyotrophic lateral sclerosis with and without cognitive impairment.Design: Performance of immunohistochemical whole central nervous system scans for evidence of pathological TDP-43 and retrospective clinical medical record review.Setting: An academic medical center.Participants: We included 64 patients with clinically and pathologically confirmed frontotemporal lobar degeneration with ubiquitinated inclusions with or without motor neuron disease and amyotrophic lateral sclerosis with or without cognitive impairment.Main Outcome Measure: Neuronal and glial TDP-43 pathology.Results: We found evidence of neuronal and glial TDP-43 pathology in all disease groups throughout the neuraxis, albeit with variations in the frequency, morphology, and distribution of TDP-43 lesions. Moreover, the major clinical manifestations (eg, cognitive impairments, motor neuron signs, extrapyramidal symptoms, neuropsychiatric features) were reflected by the predominant distribution and burden of TDP-43 pathology.Conclusion: These findings strongly suggest that amyotrophic lateral sclerosis, frontotemporal lobar degeneration with amyotrophic lateral sclerosis or motor neuron disease, and frontotemporal lobar degeneration with ubiquitinated inclusions are different manifestations of a multiple-system TDP-43 proteinopathy linked to similar mechanisms of neurodegeneration.