Yamashita Rika, Beck Goichi, Shigenobu Kazue, Tarutani Airi, Yonenobu Yuki, Kawai Makiko, Mori Kohji, Tahara Shinichiro, Satake Yuto, Saito Yuko, Morii Eiichi, Hasegawa Masato, Ikeda Manabu, Mochizuki Hideki, Murayama Shigeo
Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan.
Asakayama General Hospital, Osaka, Japan.
Neuropathology. 2025 Jan 14. doi: 10.1111/neup.13026.
The degeneration of pyramidal tracts has been reported in frontotemporal lobar degeneration with TDP-43 (TAR DNA-binding protein 43) pathology (FTLD-TDP) type C. Herein, we examined the detailed pathology of the primary motor area and pyramidal tracts in the central nervous system in four autopsy cases of FTLD-TDP type C, all of which were diagnosed by neuropathological, biochemical, and genomic analyses. Three patients showed right dominant atrophy of the frontal and temporal lobes, while the other patient showed left dominant atrophy. All four patients showed motor symptoms, and two patients had episodes of repeated aspiration. In the primary motor area, phosphorylated TDP-43 (p-TDP-43) or annexin A11-immunoreactive long dystrophic neurites were observed in all cases, and neuronophagia of the Betz cells was frequently observed in two of four cases. In the lower motor system, p-TDP-43 or annexin A11-positive dystrophic neurites were detected in the anterior horn of the spinal cord. Immuno-electron microscopy of the insoluble fraction extracted from all cases showed p-TDP-43 or annexin A11-labelled filaments. In FTLD-TDP type C, neurodegeneration with TDP and annexin A11 pathology was observed mainly in the upper motor neurons of both patients with right- and left predominant temporal atrophy and a short disease duration. Furthermore, a combination of TDP-43 and annexin A11 pathology was visible in the lower motor neurons, albeit less frequently. In summary, we reported the TDP-43 and annexin A11-associated involvement of anterior horn cells of the spinal cord for the first time. The degeneration of the motor system could contribute to dysphagia and aspiration pneumonia at the late stage of FTLD-TDP type C. Little or no TDP pathology was found in the corticospinal tract, unlike in FTLD-TDP type B, suggesting the occurrence of secondary degeneration in FTLD-TDP type C.
在伴有TDP - 43（TAR DNA结合蛋白43）病理改变的额颞叶变性C型（FTLD - TDP）中，已报道有锥体束变性。在此，我们检查了4例FTLD - TDP C型尸检病例中枢神经系统中初级运动区和锥体束的详细病理情况，所有病例均通过神经病理学、生物化学和基因组分析确诊。3例患者表现为右侧额叶和颞叶为主的萎缩，而另1例患者表现为左侧为主的萎缩。所有4例患者均有运动症状，2例患者有反复误吸发作。在初级运动区，所有病例均观察到磷酸化TDP - 43（p - TDP - 43）或膜联蛋白A11免疫反应性长营养不良性神经突，4例中有2例经常观察到Betz细胞的噬神经元现象。在运动系统下部，脊髓前角检测到p - TDP - 4 和膜联蛋白A11阳性的营养不良性神经突。对所有病例提取的不溶性部分进行免疫电子显微镜检查显示有p - TDP - 43或膜联蛋白A11标记的细丝。在FTLD - TDP C型中，主要在右侧和左侧颞叶萎缩为主且病程较短的患者的上运动神经元中观察到伴有TDP和膜联蛋白A11病理改变的神经变性。此外，在下运动神经元中也可见TDP - 43和膜联蛋白A11病理改变的组合，尽管频率较低。总之，我们首次报道了脊髓前角细胞与TDP - 43和膜联蛋白A11相关的受累情况。运动系统的变性可能导致FTLD - TDP C型晚期的吞咽困难和吸入性肺炎。与FTLD - TDP B型不同，在皮质脊髓束中几乎未发现或未发现TDP病理改变，提示FTLD - TDP C型存在继发性变性。
