Institute of Complex Systems (ICS-6: Structural Biochemistry), Forschungszentrum Jülich, Germany.
Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, Germany.
FEBS Lett. 2018 Feb;592(4):516-534. doi: 10.1002/1873-3468.12983. Epub 2018 Feb 8.
Early diagnosis of Alzheimer's disease (AD) is of great importance for the development of therapeutics and their application in the clinical environment. Amyloid β (Aβ) oligomers are crucial for the onset and progression of AD and represent a popular drug target, being presumably the most direct biomarker. Efforts to measure Aβ oligomers in body fluids are hampered by the low analyte concentration and presence of Aβ monomers. The surface-based fluorescence intensity distribution analysis (sFIDA) features both highly specific and sensitive oligomer quantitation as well as total insensitivity towards monomers. In this Review, we highlight structural features of oligomeric and fibrillar Aβ. Recent advancements in sFIDA assay development have been the successful automation, adaption for additional biomarkers such as α-synuclein oligomers, and significant improvement of essential assay parameters.
早期诊断阿尔茨海默病(AD)对于治疗方法的开发及其在临床环境中的应用非常重要。淀粉样蛋白β(Aβ)寡聚体对 AD 的发病和进展至关重要,是一个受欢迎的药物靶点,可能是最直接的生物标志物。在体液中测量 Aβ寡聚体的工作受到分析物浓度低和 Aβ单体存在的阻碍。基于表面的荧光强度分布分析(sFIDA)具有高度特异性和敏感的寡聚体定量以及对单体的完全不敏感。在这篇综述中,我们强调了寡聚体和纤维状 Aβ的结构特征。sFIDA 检测方法的最新进展包括成功的自动化、对其他生物标志物(如α-突触核蛋白寡聚体)的适应以及对基本检测参数的显著改进。