Department of Chemical and Biological Engineering , Korea University , Seoul 02841 , South Korea.
ACS Sens. 2019 Mar 22;4(3):595-602. doi: 10.1021/acssensors.8b01242. Epub 2019 Feb 22.
Blood-based diagnosis (hemodiagnosis) of Alzheimer's disease (AD) is emerging as a promising alternative to cerebrospinal-fluid-based methods because blood contains various kinds of AD biomarkers, including amyloid beta 1-40, 1-42, and τ (tau) protein. However, with current technology, the accuracy of the blood-plasma-based methods is relatively low compared to the traditional methods because the concentration of AD biomarkers in blood plasma is incredibly low, and diverse interference is present in blood plasma, which hinders precise detection. Here, we suggest a nanoplasmonic biosensor using gold nanorods with a chaotropic agent for precise ultrasensitive detecting of Alzheimer's disease biomarkers in human plasma. This nanoplasmonic biosensor is based on the localized surface plasmon resonance (LSPR), which is extremely sensitive to the point where it can respond to an insignificant change of the refractive index around the gold nanoparticles. Also, using guanidine hydrochloride as a chaotropic agent, we can overcome the obstacles of blood-based AD diagnostics. In more detail, this agent interrupts the network between water molecules and weakens the hydrophobic interactions between proteins, remarkably improving detection capabilities to target τ protein. By reducing the overlapping ranges between protein levels in an age-matched control and AD patients' plasma, this system can accurately diagnose AD patients. This platform also can analyze disease from mild cognitive impairment using standardized blood biomarker tau protein, which is related to Alzheimer's disease. As a result, our platform can be applied to clinical trials, and thus it has excellent potential in the medical field.
基于血液的阿尔茨海默病（AD）诊断（血液诊断）正在成为一种有前途的替代基于脑脊液的方法，因为血液中含有各种 AD 生物标志物，包括淀粉样蛋白β 1-40、1-42 和 τ（tau）蛋白。然而，由于目前的技术，与传统方法相比，基于血液-血浆的方法的准确性相对较低，因为血液中 AD 生物标志物的浓度非常低，并且血液中存在各种干扰，这阻碍了精确检测。在这里，我们提出了一种使用金纳米棒和离液剂的纳米等离子体生物传感器，用于精确超灵敏检测人血浆中的阿尔茨海默病生物标志物。这种纳米等离子体生物传感器基于局域表面等离子体共振（LSPR），对金纳米粒子周围折射率的微小变化极其敏感。此外，使用盐酸胍作为离液剂，我们可以克服基于血液的 AD 诊断的障碍。更详细地说，该试剂中断了水分子之间的网络，并削弱了蛋白质之间的疏水相互作用，显著提高了对靶蛋白 tau 的检测能力。通过减少年龄匹配对照组和 AD 患者血浆中蛋白质水平的重叠范围，该系统可以准确诊断 AD 患者。该平台还可以使用与阿尔茨海默病相关的标准化血液生物标志物 tau 蛋白来分析轻度认知障碍疾病。因此，我们的平台可以应用于临床试验，因此在医学领域具有巨大的潜力。
