Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
J Neurol Sci. 2018 Nov 15;394:99-106. doi: 10.1016/j.jns.2018.09.011. Epub 2018 Sep 12.
We evaluated the morphology of amyloid fibrils in the peripheral nervous system using biopsy or autopsy specimens from hereditary transthyretin amyloidosis patients. The impact of amyloid fibril formation on neighboring tissues was also investigated.
Sural nerve biopsy specimens from 34 patients were examined using electron microscopy. Twenty-eight patients had Val30Met mutations, and the remaining 6 patients had non-Val30Met mutations (i.e., Glu54Lys, Pro24Ser, Thr49Ala, Val71Ala, Val94Gly, and Ala97Gly). The patients with the Val30Met mutation included a case from Brazil (supposedly of Portuguese origin), 6 early-onset cases from endemic foci in Japan, and 21 late-onset cases from non-endemic areas in Japan.
Long amyloid fibers were abundant in the early-onset Val30Met cases from the Japanese endemic foci and Brazil, whereas the amyloid fibrils were generally short in the late-onset Val30Met and non-Val30Met cases. The amyloid fibrils seemed to mature from dotty structures among amorphous electron-dense extracellular materials and pull surrounding tissues during the maturation process. The distortion of Schwann cells close to amyloid fibril masses was conspicuous, particularly in cases with long amyloid fibrils. Atrophy was conspicuous in non-myelinating Schwann cells and bands of Büngner (i.e., Schwann cell subunits that previously contained myelinated axons), particularly those completely surrounded by amyloid fibrils. In contrast, the myelinated fibers tended to be only partially surrounded by amyloid fibrils and morphologically preserved due to their large size. Only a few demyelinated axons were found.
Pre-fibrillar amyloid precursors appear to play a pivotal role during the initial phase of amyloid fibril formation. The mechanical distortion and subsequent atrophy of Schwann cells resulting from the elongation of amyloid fibrils may be related to small-fiber predominant loss, which is a classical characteristic of amyloid neuropathy. Although rather rare, the destruction of myelin (i.e., demyelination) resulting from amyloid deposition may relate to nerve conduction abnormalities mimicking chronic inflammatory demyelinating polyneuropathy.
我们使用遗传性转甲状腺素淀粉样变性患者的活检或尸检标本评估了周围神经系统中淀粉样纤维的形态。还研究了淀粉样纤维形成对邻近组织的影响。
使用电子显微镜检查了 34 名患者的腓肠神经活检标本。28 名患者携带 Val30Met 突变，其余 6 名患者携带非 Val30Met 突变（即 Glu54Lys、Pro24Ser、Thr49Ala、Val71Ala、Val94Gly 和 Ala97Gly）。携带 Val30Met 突变的患者包括来自巴西（推测为葡萄牙血统）的 1 例、日本地方性病灶的 6 例早发性病例和日本非地方性病灶的 21 例晚发性病例。
日本地方性病灶和巴西的早发性 Val30Met 病例中大量存在长淀粉样纤维，而晚发性 Val30Met 和非 Val30Met 病例中的淀粉样纤维通常较短。淀粉样纤维似乎在成熟过程中从无定形电子致密细胞外物质中的点状结构中成熟，并在成熟过程中拉动周围组织。靠近淀粉样纤维团块的 Schwann 细胞变形明显，尤其是在长淀粉样纤维的情况下。非髓鞘化 Schwann 细胞和 Büngner 带（即以前含有髓鞘轴突的 Schwann 细胞亚单位）明显萎缩，尤其是完全被淀粉样纤维包围的 Schwann 细胞。相比之下，由于髓鞘纤维较大，它们往往仅部分被淀粉样纤维包围且形态保持完整。仅发现少数脱髓鞘轴突。
预纤维状淀粉样前体似乎在淀粉样纤维形成的初始阶段发挥关键作用。淀粉样纤维的伸长引起 Schwann 细胞的机械扭曲和随后的萎缩可能与小纤维为主的丧失有关，这是淀粉样神经病的经典特征。尽管相当罕见，但淀粉样沉积引起的髓鞘破坏（即脱髓鞘）可能与类似于慢性炎症性脱髓鞘性多发性神经病的神经传导异常有关。
