TDP-43 proteinopathy and motor neuron disease in chronic traumatic encephalopathy.
TDP-43 proteinopathy and motor neuron disease in chronic traumatic encephalopathy.
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DOI：
10.1097/nen.0b013e3181ee7d85
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发表时间：
2010-09
影响因子：
3.2
通讯作者：
Budson AE
中科院分区：
文献类型：
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作者：
McKee AC;Gavett BE;Stern RA;Nowinski CJ;Cantu RC;Kowall NW;Perl DP;Hedley-Whyte ET;Price B;Sullivan C;Morin P;Lee HS;Kubilus CA;Daneshvar DH;Wulff M;Budson AE
流行病学证据表明，肌萎缩侧索硬化症的发病率增加与头部损伤有关。重复性头部损伤也与慢性创伤性脑病（CTE）的发展有关，CTE是一种以相对缺乏β-淀粉样蛋白沉积的整个大脑神经原纤维缠结为特征的脑病。我们检查了12例CTE，其中10例发现广泛存在约43 kd的TAR dna结合蛋白（TDP-43）蛋白病变，影响额叶和颞叶、内侧颞叶、基底神经节、间脑和脑干。三名患有CTE的运动员在死前几年也出现了进行性运动神经元疾病，表现为严重无力、萎缩、痉挛和束状。3例脊髓除tau神经原纤维改变、运动神经元丢失、皮质脊髓束变性外，还可见丰富的tdp -43阳性包涵体和神经突。与CTE相关的TDP-43蛋白病变与伴有TDP-43包涵体的额颞叶变性相似，即大脑的广泛区域受到影响。与伴有TDP-43包涵体的额颞叶变性类似，在一些CTE患者中，TDP-43蛋白病变可累及脊髓，并与运动神经元疾病相关。这是第一个在碰撞运动中经历的重复性头部创伤可能与运动神经元疾病的发展有关的病理证据。
Epidemiological evidence suggests that the incidence of amyotrophic lateral sclerosis is increased in association with head injury. Repetitive head injury is also associated with the development of chronic traumatic encephalopathy (CTE), a tauopathy characterized by neurofibrillary tangles throughout the brain in the relative absence of β-amyloid deposits. We examined 12 cases of CTE and, in 10, found a widespread TAR DNA-binding protein of approximately 43 kd (TDP-43) proteinopathy affecting the frontal and temporal cortices, medial temporal lobe, basal ganglia, diencephalon, and brainstem. Three athletes with CTE also developed a progressive motor neuron disease with profound weakness, atrophy, spasticity, and fasciculations several years before death. In these 3 cases, there were abundant TDP-43–positive inclusions and neurites in the spinal cord in addition to tau neurofibrillary changes, motor neuron loss, and corticospinal tract degeneration. The TDP-43 proteinopathy associated with CTE is similar to that found in frontotemporal lobar degeneration with TDP-43 inclusions, in that widespread regions of the brain are affected. Akin to frontotemporal lobar degeneration with TDP-43 inclusions, in some individuals with CTE, the TDP-43 proteinopathy extends to involve the spinal cord and is associated with motor neuron disease. This is the first pathological evidence that repetitive head trauma experienced in collision sports might be associated with the development of a motor neuron disease.