Metabolism of amyloid proteins and methods for detecting amyloid proteins

系统性AA淀粉样变性是慢性炎症性疾病，尤其是类风湿性关节炎最严重的并发症之一。众所周知，淀粉样增强因子(AEF)类似于一种传染性的普恩蛋白，在AA淀粉样变性中起着传播性因子的作用。然而，AEF如何在体内传递AA淀粉样变性仍未完全阐明。在本研究中，我们利用AA淀粉样变性的小鼠转移模型，致力于寻找循环中无细胞形式的AEF及其携带者。我们首次确定系统性AA淀粉样变性小鼠的血液和血浆中存在循环中的无细胞AEF。第二，我们建立了含有来自血清淀粉样蛋白A的AA类淀粉样寡聚体的血浆外体具有AEF活性，并且可以通过类病毒机制传递全身性AA淀粉样变性。这些新的发现应该为系统淀粉样变的传播机制提供洞察力。我们之前报道了两例老年扁尾猴(CerCopithecus…更多的Atheiops)自发地发展为TTR淀粉样变性，并表现出类似于人类TTR淀粉样变性的临床症状。然而，猕猴TTR淀粉样变性的发病机制及其与人类疾病的关系仍有待阐明。本研究的目的是阐明猕猴TTR淀粉样变性的发病机制，并验证其与人类TTR淀粉样变性的病理关系。首先，我们利用120多个不同灵长类动物的组织标本以及马尾猴和食蟹猕猴的临床心脏表现，通过理化检查发现，老年马尾猴发生了TTR淀粉样变性，主要导致心功能障碍，而其他非人类灵长类动物既没有表现出TTR淀粉样蛋白沉积，也没有表现出心功能障碍。接下来，我们确定黑猩猩具有物种特有的Ttr等位基因。综上所述，我们认为老年马尾猴类似于人类TTR淀粉样变性，是研究这一人类遗传性疾病的珍贵物种。较少

Systemic AA amyloidosis is one of the most severe complications of chronic inflammatory disorders, particularly rheumatoid arthritis. It is well known that, similar to an infectious prion protein, amyloid-enhancing factor (AEF) acts as a transmissible agent in AA amyloidosis. However, how AEF transmits AA amyloidosis in vivo remained to be fully elucidated. In the present study, we focused on finding cell-free forms of AEF and its carriers in circulation by using the murine transfer model of AA amyloidosis. We first determined that circulating cell-free AEF existed in blood and plasma in mice with systemic AA amyloidosis. Second, we established that plasma exosomes containing AA amyloid oligomers derived from serum amyloid A had AEF activity and could transmit systemic AA amyloidosis via a prion-like mechanism. These novel findings should provide insights into the transmission mechanism of systemic amyloidoses.We previously reported that two cases of aged vervet monkeys (Cercopithecus … More aethiops) spontaneously developed TTR amyloidosis and showed clinical symptoms mimicking human TTR amyloidosis. However, the pathogenesis of TTR amyloidosis in vervet monkeys and relationship to the human disease remained to be elucidated. The aims of the present study were to elucidate the pathogenesis of TTR amyloidosis in the vervet monkeys, and to verify pathological relationship to the human TTR amyloidosis. First, using over 120 tissue specimens of various primates and clinical cardiac findings of vervet monkeys and crab-eating macaques, we showed that aged vervet monkeys developed TTR amyloidosis mainly causing cardiac dysfunction by means of physicochemical examinations, but other non-human primates showed neither TTR amyloid deposits nor cardiac dysfunctions. Next, we determined that vervet monkeys had the species-specific TTR allele. Taken together, we propose that the aged vervet monkeys mimic the human TTR amyloidosis and the monkey is a precious species as an animal model for this hereditary disease of human. Less