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Application of an Amyloid Beta Oligomer Standard in the sFIDA Assay

机译:淀粉样β寡聚体标准品在sFIDA分析中的应用

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摘要

Still, there is need for significant improvements in reliable and accurate diagnosis for Alzheimer's disease (AD) at early stages. It is widely accepted that changes in the concentration and conformation of amyloid-β (Aβ) appear several years before the onset of first symptoms of cognitive impairment in AD patients. Because Aβ oligomers are possibly the major toxic species in AD, they are a promising biomarker candidate for the early diagnosis of the disease. To date, a variety of oligomer-specific assays have been developed, many of them ELISAs. Here, we demonstrate the sFIDA assay, a technology highly specific for Aβ oligomers developed toward single particle sensitivity. By spiking stabilized Aβ oligomers to buffer and to body fluids from control donors, we show that the sFIDA readout correlates with the applied concentration of stabilized oligomers diluted in buffer, cerebrospinal fluid (CSF), and blood plasma over several orders of magnitude. The lower limit of detection was calculated to be 22 fM of stabilized oligomers diluted in PBS, 18 fM in CSF, and 14 fM in blood plasma.
机译:仍然需要在早期阶段对阿尔茨海默氏病(AD)的可靠和准确的诊断进行重大改进。公认的是,AD患者在出现认知障碍的第一症状之前几年,淀粉样β(Aβ)浓度和构象的变化就出现了。由于Aβ低聚物可能是AD中的主要毒性物质,因此它们是该疾病早期诊断的有前途的生物标志物候选物。迄今为止,已经开发了多种寡聚物特异性测定法,其中许多是ELISA。在这里,我们演示了sFIDA分析,这是一种对Aβ低聚物具有高度特异性的技术,已朝着单粒子敏感性发展。通过加标稳定的Aβ低聚物以缓冲液和来自对照供体的体液,我们显示sFIDA读数与在缓冲液,脑脊液(CSF)和血浆中稀释的稳定化低聚物的应用浓度相关,幅度超过几个数量级。计算的下限为在PBS中稀释的22 fM稳定化低聚物,在CSF中的18 fM和在血浆中的14 fM。

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