Department of Electrical and Computer Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.
Biomedical Engineering Research Center, Smart Healthcare Research Institute, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul 06351, Republic of Korea.
Biosensors (Basel). 2024 Oct 17;14(10):510. doi: 10.3390/bios14100510.
Monitoring the progression of Alzheimer's disease (AD) is crucial for mitigating dementia symptoms, alleviating pain, and improving mobility. Traditionally, AD biomarkers like amyloid plaques are predominantly identified in cerebrospinal fluid (CSF) due to their concentrated presence. However, detecting these markers in blood is hindered by the blood-brain barrier (BBB), resulting in lower concentrations. To address this challenge and identify pertinent AD biomarkers-specifically amyloid plaques and apolipoprotein E4 (ApoE4)-in blood plasma, we propose an innovative approach. This involves enhancing a screen-printed carbon electrode (SPCE) with an immobilization matrix comprising gold nanostars (AuNSs) coated with chitosan. Morphological and electrical analyses confirmed superior dispersion and conductivity with 0.5% chitosan, supported by UV-Vis spectroscopy, cyclic voltammetry, and Nyquist plots. Subsequent clinical assays measured electrical responses to quantify amyloid-β 42 (Aβ42) (15.63-1000 pg/mL) and APoE4 levels (0.41 to 40 ng/mL) in human blood plasma samples. Differential pulse voltammetry (DPV) responses exhibited peak currents proportional to biomarker concentrations, demonstrating high linear correlations (0.985 for Aβ42 and 0.919 for APoE4) with minimal error bars. Cross-reactivity tests with mixed solutions of amyloid-β 40 (Aβ40), Aβ42, and ApoE4 indicated minimal interference between biomarkers (<3% variation), further confirming the high specificity of the developed sensor. Validation studies demonstrated a strong concurrence with the gold-standard enzyme-linked immunosorbent assay (ELISA), while interference tests indicated a minimal variation in peak currents. This improved device presents promising potential as a point-of-care system, offering a less invasive, cost-effective, and simplified approach to detecting and tracking the progression of AD. The substantial surface binding area further supports the efficacy of our method, offering a promising avenue for advancing AD diagnostics.
监测阿尔茨海默病（AD）的进展对于减轻痴呆症状、缓解疼痛和提高活动能力至关重要。传统上，由于淀粉样斑块在脑脊液（CSF）中浓度较高，AD 生物标志物主要在 CSF 中进行检测。然而，由于血脑屏障（BBB）的存在，这些标志物在血液中的检测受到阻碍，导致浓度降低。为了解决这一挑战，并在血液血浆中检测到相关的 AD 生物标志物，特别是淀粉样斑块和载脂蛋白 E4（ApoE4），我们提出了一种创新的方法。该方法涉及用包含涂有壳聚糖的金纳米星（AuNSs）的固定基质增强丝网印刷碳电极（SPCE）。形态和电学分析证实，在 0.5%壳聚糖的支持下，AuNSs 具有更好的分散性和导电性，这一点得到了紫外可见光谱、循环伏安法和奈奎斯特图的支持。随后的临床检测测量了电响应，以量化人血浆样本中的淀粉样β 42（Aβ42）（15.63-1000 pg/mL）和 ApoE4 水平（0.41 至 40 ng/mL）。差分脉冲伏安法（DPV）响应显示出与生物标志物浓度成正比的峰电流，表现出高线性相关性（Aβ42 为 0.985，ApoE4 为 0.919），误差棒最小。用混合的淀粉样β 40（Aβ40）、Aβ42 和 ApoE4 溶液进行的交叉反应测试表明，生物标志物之间的干扰最小（<3%的变化），进一步证实了所开发传感器的高特异性。验证研究表明，与金标准酶联免疫吸附测定（ELISA）具有很强的一致性，而干扰测试表明峰电流的变化很小。这种改进的设备具有作为即时护理系统的巨大潜力，提供了一种侵入性更小、更具成本效益和简化的方法，用于检测和跟踪 AD 的进展。较大的表面结合面积进一步支持了我们方法的有效性，为 AD 诊断的发展提供了一个很有前途的途径。
