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利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在过去的一年里，我们继续并扩大了对A蛋白多聚体的菌株样结构变体的分析。我们已经证明，与阿尔茨海默氏症不同，非人类灵长类动物中自然产生的A？不会以高亲和力结合A？结合配体PIB，尽管有相同的氨基酸序列。这一发现表明，PIB可能识别多聚体A？上的一个多态位点。 出乎意料的是，在这次调查的过程中，我们还发现了一例阿尔茨海默病患者，其A？水平非常高，但高亲和力的PIB结合可以忽略不计，这表明结合位点可能在患有该疾病的人中有所不同。这一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，这些形状可以控制它们的致病性质。

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.