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。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 中心，但不一定是研究者所在的机构。 在过去的一年中，我们继续并扩大了对蛋白A的多聚体聚集体的菌株样结构变体的分析。 我们已经表明，与阿尔茨海默病不同，非人灵长类动物中天然存在的A <$不会以高亲和力结合A <$-结合配体PIB，尽管氨基酸序列相同。这一发现表明PIB可能识别多聚体A？上的多态性位点。 出乎意料的是，在这项研究的过程中，我们还发现了一个阿尔茨海默病的病例，A？水平非常高，但可以忽略不计的高亲和力PIB结合，这表明结合位点可能在患有这种疾病的人中有所不同。这些发现支持了越来越多的证据，即蛋白质聚集体可能呈现出几种多维形状，这些形状可以控制其致病性质。

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. In the past year, we have continued and expanded our analysis of strain-like structural variants of multimeric aggregates of the protein A¿. We have shown that, unlike in Alzheimer's disease, naturally occurring A¿ in nonhuman primates does not bind the A¿-binding ligand PIB with high affinity, despite an identical amino acid sequence. This finding suggests that PIB may recognize a polymorphic site on multimeric A¿. Unexpectedly, in the course of this investigation, we also discovered a single case of Alzheimer's disease with very high A¿ levels, yet negligible high-affinity PIB binding, indicating that the binding site may vary among humans with the disease. The findings support growing evidence that protein aggregates may assume several multidimensional shapes that could govern their pathogenic nature.