ALZHEIMER'S DISEASE: MODELING PATHOLOGIC STRAIN-LIKE VARIANTS OF MULTIMERIC A?

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 现在有强有力的证据表明，阿尔茨海默病是由蛋白质错误地相互结合在一起，在大脑中形成有毒的聚集体引起的。驱动这一过程的蛋白质被称为A？。人们对活体大脑中致病蛋白的种类知之甚少。 我们已经开发出一种新的方法，使蛋白质在大脑中聚集，基于一个简单的原理，即具有特定异常形状的特定蛋白质分子可以通过类似于种子结晶的过程使同一分子的正常版本变得异常。 最近，我们发现，已经开发出用于成像阿尔茨海默病中A <$的分子实际上可以区分A <$的有毒和良性聚集体。 因此，A <$结合剂有可能区分A <$的结构变体，这些变体可能对大脑有不同的毒性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There is now strong evidence that Alzheimer's disease is caused by proteins that mistakenly bind to one another to form toxic aggregates in the brain. The protein that drives this process is known as A¿. Little is known about the strains of disease-causing proteins in the living brain. We have developed a new way of causing proteins to aggregate in the brain based on the simple principle that a particular protein molecule with a particular abnormal shape can cause normal versions of the same molecule to become abnormal by a process analagous to seeded crystallization. Recently we have found that molecules that have been developed to image A¿ in Alzheimer's disease may actually distinguish between toxic and benign aggregates of A¿. A¿-binding agents thus have the potential to distinguish among stuctural variants of A¿ that may be differentially toxic to the brain.