Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
Department of Neurology, Hokuriku Brain and Neuromuscular Disease Center, National Hospital Organization Iou National Hospital, Kanazawa, Japan.
Neuropathology. 2020 Dec;40(6):606-610. doi: 10.1111/neup.12673. Epub 2020 Aug 9.
We report for the first time the presence of phosphorylated transactivation response DNA-binding protein of 43 kDa (p-TDP-43)-immunoreactive cytoplasmic inclusions in Schwann cells in an autopsy case of sporadic amyotrophic lateral sclerosis (ALS). An 81-year-old woman with no family history of neuromuscular disorders noticed difficulty in handling chopsticks due to weakness of the hands. She then developed weakness of the lower and upper limbs and dyspnea. Neurological examination at the age of 83 years revealed disorientation, severe weakness of the facial muscles, tongue, neck and extremities, and fasciculations in the thighs. She exhibited hyperactive jaw jerk and lower limb deep tendon reflexes and normal upper limb deep tendon reflexes, and left extensor plantar response was observed. The patient was diagnosed as having sporadic ALS. An autopsy performed at the age of 84 years revealed widespread p-TDP-43-immunoreactive neuronal and glial cytoplasmic inclusions in the cerebrum, brain stem, and spinal cord, in addition to some Bunina bodies. Moreover, a small number of p-TDP-43-immunoreactive inclusions were found in the facial or accoustic nerve (indistinguishable), spinal cord anterior roots, cauda equina, and peripheral nerves in the dorsal root ganglia. Immunohistochemical staining for p-TDP-43 revealed just a few p-TDP-43-immunoreactive inclusions surrounding axons in the cervical and lumbar anterior roots. Double immunofluorescence analysis revealed that these inclusions were co-localized with S-100 protein β, suggesting that these inclusions were localized in the cytoplasm of Schwann cells. The peripheral nervous system including Schwann cells may be involved in TDP-43 pathology in ALS.
我们首次报道了散发性肌萎缩侧索硬化症（ALS）尸检病例中 Schwann 细胞中存在磷酸化反式激活反应 DNA 结合蛋白 43kDa（p-TDP-43）免疫反应性细胞质内含物。一名 81 岁女性，无神经肌肉疾病家族史，因手部无力而注意到难以使用筷子。随后，她出现了下肢和上肢无力以及呼吸困难。83 岁时的神经检查显示定向障碍、面部肌肉、舌、颈部和四肢严重无力，大腿出现肌束颤动。她表现出下颌反射亢进和下肢深腱反射，上肢深腱反射正常，观察到左侧伸性跖反射。该患者被诊断为散发性 ALS。84 岁时进行的尸检显示，大脑、脑干和脊髓中存在广泛的 p-TDP-43 免疫反应性神经元和神经胶质细胞质内含物，此外还有一些 Bunina 体。此外，在面神经或听神经（无法区分）、脊髓前根、马尾和背根神经节中的周围神经中发现了少量的 p-TDP-43 免疫反应性内含物。p-TDP-43 的免疫组织化学染色显示，仅在颈段和腰段前根的轴突周围存在少量 p-TDP-43 免疫反应性内含物。双重免疫荧光分析显示，这些内含物与 S-100 蛋白 β 共定位，表明这些内含物位于 Schwann 细胞的细胞质中。包括 Schwann 细胞在内的周围神经系统可能参与了 ALS 中 TDP-43 病理学。
