Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
Hum Pathol. 2011 Feb;42(2):236-43. doi: 10.1016/j.humpath.2010.06.014. Epub 2010 Nov 5.
Wild-type transthyretin is inherently an amyloidogenic protein, but its contribution to the formation of amyloid fibrils remains unclear in familial amyloid polyneuropathy patients. Our aim in this study was to elucidate the ratio of wild-type transthyretin in amyloid deposits in familial amyloid polyneuropathy patients. Abdominal fat amyloid fibrils in 44 familial amyloid polyneuropathy patients with amyloidogenic transthyretin Val30Met who had not undergone liver transplantation were examined. The amyloid fibrils were extracted from abdominal fat tissues and the composition ratios of wild-type and variant transthyretin were analyzed with liquid chromatography tandem mass spectrometry. The amyloid fibrils in abdominal fat tissues were composed of not only variant but also wild-type transthyretin in most patients (mean ratio, 40.7% ± 27.5%). The composition ratios of wild-type transthyretin in patients older than 50 years were significantly higher than those in patients younger than 50 (50.7% ± 26.9% versus 30.7 ± 24.8%). Our results indicate that wild-type transthyretin significantly contributes to the formation of amyloid fibrils in familial amyloid polyneuropathy patients with amyloidogenic transthyretin Val30Met, and its contribution tends to increase in older patients, suggesting that aging may play an important role in wild-type transthyretin-derived amyloid fibril formation in familial amyloid polyneuropathy patients. This is the first report showing the relationship between wild-type transthyretin deposition and aging in familial amyloid polyneuropathy patients. In addition, wild-type transthyretin may be more strongly amyloidogenic than previously considered because it is detectable even in amyloid fibrils isolated from young familial amyloid polyneuropathy patients.
野生型转甲状腺素蛋白本身就是一种淀粉样蛋白原性蛋白，但在家族性淀粉样多发性神经病患者中，其对淀粉样纤维形成的贡献仍不清楚。本研究旨在阐明家族性淀粉样多发性神经病患者淀粉样沉积物中野生型转甲状腺素蛋白的比例。检查了 44 名未接受肝移植的携带淀粉样蛋白原性转甲状腺素蛋白 Val30Met 的家族性淀粉样多发性神经病患者的腹部脂肪淀粉样纤维。从腹部脂肪组织中提取淀粉样纤维，并通过液相色谱串联质谱分析野生型和变异型转甲状腺素蛋白的组成比例。大多数患者的腹部脂肪组织中的淀粉样纤维不仅由变异型，而且由野生型转甲状腺素蛋白组成（平均比例为 40.7%±27.5%）。年龄大于 50 岁的患者中野生型转甲状腺素蛋白的组成比例明显高于年龄小于 50 岁的患者（50.7%±26.9%比 30.7%±24.8%）。我们的结果表明，野生型转甲状腺素蛋白在携带淀粉样蛋白原性转甲状腺素蛋白 Val30Met 的家族性淀粉样多发性神经病患者中显著促进淀粉样纤维的形成，并且在老年患者中的贡献有增加的趋势，提示衰老可能在家族性淀粉样多发性神经病患者的野生型转甲状腺素蛋白衍生的淀粉样纤维形成中发挥重要作用。这是首次报道家族性淀粉样多发性神经病患者中野生型转甲状腺素蛋白沉积与衰老之间的关系。此外，由于即使在从年轻的家族性淀粉样多发性神经病患者中分离出的淀粉样纤维中也能检测到野生型转甲状腺素蛋白，因此它可能比以前认为的更具淀粉样蛋白原性。
