Detection of Misfolded Aβ Oligomers for Sensitive Biochemical Diagnosis of Alzheimer's Disease
Detection of Misfolded Aβ Oligomers for Sensitive Biochemical Diagnosis of Alzheimer's Disease
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DOI：
10.1016/j.celrep.2014.02.031
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发表时间：
2014-04-01
期刊：
影响因子：
8.8
通讯作者：
Soto, Claudio
中科院分区：
文献类型：
--
作者：
Salvadores, Natalia;Shahnawaz, Mohammad;Soto, Claudio
阿尔茨海默病（AD）的诊断受到缺乏早期，敏感和客观的实验室检查的阻碍。我们描述了一种基于特异性检测错误折叠的A β寡聚体的AD生化诊断的灵敏方法，该寡聚体在AD发病机制中起着核心作用。蛋白质错误折叠循环扩增试验（A β-PMCA）利用A β寡聚体的功能特性来接种单体A β的聚合。β-PMCA允许检测低至3 fmol的A β寡聚体。最重要的是，使用脑脊液，我们能够区分AD患者与受各种其他神经退行性疾病或非退行性神经系统疾病影响的对照个体，总体敏感性为90%，特异性为92%。这些发现为开发用于AD诊断的高度敏感和特异性生化测试提供了原理验证基础。
Alzheimer's disease (AD) diagnosis is hampered by the lack of early, sensitive, and objective laboratory tests. We describe a sensitive method for biochemical diagnosis of AD based on specific detection of misfolded A beta oligomers, which play a central role in AD pathogenesis. The protein misfolding cyclic amplification assay (A beta-PMCA), exploits the functional property of A beta oligomers to seed the polymerization of monomeric A beta. A beta-PMCA allowed detection of as little as 3 fmol of A beta oligomers. Most importantly, using cerebrospinal fluid, we were able to distinguish AD patients from control individuals affected by a variety of other neurodegenerative disorders or nondegenerative neurological diseases with overall sensitivity of 90% and specificity of 92%. These findings provide the proof-of-principle basis for developing a highly sensitive and specific biochemical test for AD diagnosis.