Schwann cell and endothelial cell damage in transthyretin familial amyloid polyneuropathy
Schwann cell and endothelial cell damage in transthyretin familial amyloid polyneuropathy
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DOI：
10.1212/wnl.0000000000003362
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发表时间：
2016-11-22
期刊：
影响因子：
9.9
通讯作者：
Sobue, Gen
中科院分区：
文献类型：
--
作者：
Koike, Haruki;Ikeda, Shohei;Sobue, Gen
目的：用电镜观察雪旺细胞和神经内膜微血管的形态。方法：对 49 例伴甲状腺素运载蛋白 Val30Met 突变的家族性淀粉样多发性神经病 (FAP) 患者的腓肠神经活检标本进行评估。患者包括来自流行病灶的 11 例早发病例和来自非流行地区的 38 例晚发病例。结果：神经纤维丢失伴或不伴邻近淀粉样蛋白沉积是一个共同特征。早发病例中淀粉样蛋白沉积量与神经纤维损失程度的关系大于晚发病例。与淀粉样原纤维相对应的雪旺细胞，特别是非髓鞘雪旺细胞的萎缩在早发病例中比晚发病例中更为明显。与 37 名营养性/酒精性神经病患者相比，FAP 患者的内皮细胞核、内皮细胞分布和闭塞微血管的数量显着增加（分别 p < 0.05、0.01 和 0.01）。无论是否存在淀粉样蛋白沉积，在 FAP 患者中也更频繁地发现血神经屏障破坏的发现，例如紧密连接丢失和内皮细胞开窗 (p < 0.001)。 结论：这些发现表明，淀粉样原纤维的直接损伤会导致雪旺细胞损伤，导致早发病例特有的小纤维轴突主要丢失。此外，血管病变可能参与神经病变的发病机制，特别是在晚发病例中。
Objective: To examine the morphology of Schwann cells and endoneurial microvessels with electron microscopy.Methods: Sural nerve biopsy specimens from 49 patients with familial amyloid polyneuropathy (FAP) with transthyretin Val30Met mutation were assessed. Patients included 11 early-onset cases from endemic foci and 38 late-onset cases from nonendemic areas.Results: Loss of nerve fibers with or without neighboring amyloid deposition was a common feature. The amount of amyloid deposition was greater relative to the extent of nerve fiber loss in early-onset cases than in late-onset cases. The atrophy of Schwann cells, particularly non-myelinating Schwann cells, that were apposed to amyloid fibrils was more conspicuous in early-onset cases than in late-onset cases. The numbers of endothelial cell nuclei, endothelial cell profiles, and occluded microvessels were significantly increased in the patients with FAP compared with 37 patients with nutritional/alcoholic neuropathies (p < 0.05, 0.01, and 0.01, respectively). Findings suggestive of the disruption of blood-nerve barriers such as the loss of tight junctions and the fenestration of endothelial cells were also found more frequently in the patients with FAP (p < 0.001), regardless of the presence or absence of amyloid deposition.Conclusions: These findings suggest that direct insult of amyloid fibrils causes Schwann cell damage, resulting in the predominant loss of small-fiber axons characteristic of early-onset cases. In addition, vasculopathy may participate in the pathogenesis of neuropathy, particularly in late-onset cases.