Prion-Seeding Activity Is widely Distributed in Tissues of Sporadic Creutzfeldt-Jakob Disease Patients.

Human prion diseases are neurodegenerative disorders caused by abnormally folded prion proteins in the central nervous system. These proteins can be detected using the quaking-induced conversion assay. Compared with other bioassays, this assay is extremely sensitive and was used in the present study to determine prion distribution in sporadic Creutzfeldt-Jakob disease patients at autopsy. Although infectivity of the sporadic form is thought to be restricted within the central nervous system, results showed that prion-seeding activities reach 106/g from a 50% seeding dose in non-neuronal tissues, suggesting that prion-seeding activity exists in non-neural organs, and we suggested that non-neural tissues of 106/g SD50 did not exist the infectivity. Prion-seeding activities reach 106/g from a 50% seeding dose in non-neuronal tissues. Results suggest that prion-seeding activity exists in neural and non-neural organs. A major problem for the diagnosis and management of human prion diseases is the lack of rapid and high-sensitive assays to measure low prion levels. Recent studies have tried to measure prion concentrations in non-neuronal tissues, but prion levels were not sufficient. Therefore, we developed the RT-QuIC method to measure prion-seeding activity in the non-neuronal, human tissues. The SD50 levels in the spleen, kidney, lung, and liver were 5.0–6.5, with different SD50 levels in the individual cases.

人类朊病毒疾病是由中枢神经系统中异常折叠的朊病毒蛋白引起的神经退行性疾病。这些蛋白可以使用震摇诱导转化检测法进行检测。与其他生物检测方法相比，该检测法极其灵敏，在本研究中被用于确定散发性克雅氏病患者尸检时朊病毒的分布。尽管散发性克雅氏病的传染性被认为局限于中枢神经系统，但结果显示，在非神经组织中，朊病毒种子活性从50%种子剂量达到10⁶/克，这表明朊病毒种子活性存在于非神经器官中，并且我们提出10⁶/克半数种子剂量（SD50）的非神经组织不存在传染性。 在非神经组织中，朊病毒种子活性从50%种子剂量达到10⁶/克。 结果表明，朊病毒种子活性存在于神经和非神经器官中。 人类朊病毒疾病诊断和管理的一个主要问题是缺乏快速且高灵敏度的检测方法来测量低水平的朊病毒。近期研究试图测量非神经组织中的朊病毒浓度，但朊病毒水平不足。因此，我们开发了实时震颤诱导转化（RT - QuIC）方法来测量非神经的人体组织中的朊病毒种子活性。脾脏、肾脏、肺和肝脏中的半数种子剂量（SD50）水平为5.0 - 6.5，不同病例中的SD50水平有所不同。