Department of Electronic Engineering, Gachon University, Seongnam-si, Gyeonggi-do 13120, Korea.
Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon 21999, Korea.
Sensors (Basel). 2021 Jan 25;21(3):788. doi: 10.3390/s21030788.
Aggregation of amyloid-β (aβ) peptides into toxic oligomers, fibrils, and plaques is central in the molecular pathogenesis of Alzheimer's disease (AD) and is the primary focus of AD diagnostics. Disaggregation or elimination of toxic aβ aggregates in patients is important for delaying the progression of neurodegenerative disorders in AD. Recently, 4-(2-hydroxyethyl)-1-piperazinepropanesulfonic acid (EPPS) was introduced as a chemical agent that binds with toxic aβ aggregates and transforms them into monomers to reduce the negative effects of aβ aggregates in the brain. However, the mechanism of aβ disaggregation by EPPS has not yet been completely clarified. In this study, an electrochemical impedimetric immunosensor for aβ diagnostics was developed by immobilizing a specific anti-amyloid-β (aβ) antibody onto a self-assembled monolayer functionalized with a new interdigitated chain-shaped electrode (anti-aβ/SAM/ICE). To investigate the ability of EPPS in recognizing AD by extricating aβ aggregation, commercially available aβ aggregates (aβ) were used. Electrochemical impedance spectroscopy was used to probe the changes in charge transfer resistance (R) of the immunosensor after the specific binding of biosensor with aβ. The subsequent incubation of the aβ complex with a specific concentration of EPPS at different time intervals divulged AD progression. The decline in the R of the immunosensor started at 10 min of EPPS incubation and continued to decrease gradually from 20 min, indicating that the accumulation of aβ on the surface of the anti-aβ/SAM/ICE sensor has been extricated. Here, the kinetic disaggregation rate value of aβ was found to be 0.038. This innovative study using electrochemical measurement to investigate the mechanism of aβ disaggregation by EPPS could provide a new perspective in monitoring the disaggregation periods of aβ from oligomeric to monomeric form, and then support for the prediction and handling AD symptoms at different stages after treatment by a drug, EPPS.
淀粉样蛋白-β (aβ) 肽聚集形成毒性寡聚体、纤维和斑块是阿尔茨海默病 (AD) 分子发病机制的核心，也是 AD 诊断的主要焦点。在患者中，使毒性 aβ 聚集物解聚或消除对于延缓 AD 中神经退行性疾病的进展很重要。最近，4-(2-羟乙基)-1-哌嗪丙烷磺酸 (EPPS) 被引入作为一种化学试剂，它与毒性 aβ 聚集物结合，并将其转化为单体，以减少 aβ 聚集物在大脑中的负面影响。然而，EPPS 使 aβ 解聚的机制尚未完全阐明。在这项研究中，通过将特异性抗淀粉样蛋白-β (aβ) 抗体固定在自组装单层上，开发了用于 aβ 诊断的电化学阻抗免疫传感器，该自组装单层由新的叉指链状电极 (anti-aβ/SAM/ICE) 功能化。为了研究 EPPS 通过提取 aβ 聚集物来识别 AD 的能力，使用了市售的 aβ 聚集物 (aβ)。电化学阻抗谱用于探测生物传感器与 aβ 特异性结合后电荷转移电阻 (R) 的变化。随后，将 aβ 复合物与不同浓度的 EPPS 在不同时间间隔孵育，以揭示 AD 的进展。在 EPPS 孵育 10 分钟时，免疫传感器的 R 开始下降，并从 20 分钟开始逐渐持续下降，表明 aβ 在 anti-aβ/SAM/ICE 传感器表面的积累已被提取。这里，发现 aβ 的动力学解聚速率 值为 0.038。这项使用电化学测量来研究 EPPS 使 aβ 解聚的机制的创新研究，为监测 aβ 从寡聚体到单体形式的解聚期提供了新的视角，然后为监测治疗后不同阶段 AD 症状的预测和处理提供支持。
