Shedding, retention and spreading of chronic wasting disease prions in the environment

摘要 阿尔茨海默病（AD）是最常见的痴呆类型，也是世界上第六大死亡原因。 美国的AD的主要病理特征是错误折叠形式的淀粉样β蛋白在脑中的沉积 （A β）和tau蛋白。令人信服的证据表明，这些蛋白质具有以下几个特征： 传染性朊病毒，包括其在实验动物中的传播和疾病传播机制。 考虑到朊病毒疾病可以通过受污染的材料传播（ 目前的R01申请），人们对AD的病理特征是否可以传播提出了担忧 以类似的方式。在本申请中，我们将使用体外和体内测定来探索这种可能性。具体地说， A β和tau暴露的材料传播病理构象的能力将通过以下方式进行测试：（i）体外 聚集测定，和（ii）使用污染的外科手术器械的外科手术。同时，我们将 探索临床和研究环境中使用的不同去污方法是否能够减少 错误折叠蛋白质的结合及其繁殖能力。这项研究的结果可以帮助解决一个 一个重要的问题，涉及朊病毒样传输的错误折叠蛋白质，并可能是有用的其他脑 和系统性蛋白质病。

ABSTRACT Alzheimer’s disease (AD) is the most common type of dementia and the 6th leading cause of death in the United States. The main pathological features of AD are the brain deposition of misfolded forms of amyloid-beta (Aβ) and tau proteins. Compelling evidence demonstrate that these proteins share several characteristics with infectious prions, including their mechanisms of spread and disease transmission in experimental animals. Considering that prion diseases can be transmitted through contaminated materials (one of the focuses of the current R01 application), concerns have been raised on whether pathological features of AD can be transmitted in a similar way. In this application, we will explore this possibility using in vitro and in vivo assays. Specifically, the ability of Aβ- and tau- exposed materials to spread pathological conformations will be tested by: (i) in vitro aggregation assays, and (ii) surgical procedures using contaminated surgical instruments. In parallel, we will explore whether different decontamination methods used in clinical and research settings are able to decrease binding of misfolded proteins and their ability to propagate. Results from this research could help to address an important concern related to the prion-like transmission of misfolded proteins and may be useful for other cerebral and systemic proteinopathies.