Integrated Science and Engineering Division, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Republic of Korea.
Department of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Republic of Korea.
Sci Adv. 2019 Apr 17;5(4):eaav1388. doi: 10.1126/sciadv.aav1388. eCollection 2019 Apr.
Detection of amyloid-β (Aβ) aggregates contributes to the diagnosis of Alzheimer disease (AD). Plasma Aβ is deemed a less invasive and more accessible hallmark of AD, as Aβ can penetrate blood-brain barriers. However, correlations between biofluidic Aβ concentrations and AD progression has been tenuous. Here, we introduce a diagnostic technique that compares the heterogeneous and the monomerized states of Aβ in plasma. We used a small molecule, EPPS [4-(2-hydroxyethyl)-1-piperazinepropanesulfonic acid], to dissociate aggregated Aβ into monomers to enhance quantification accuracy. Subsequently, Aβ levels of EPPS-treated plasma were compared to those of untreated samples to minimize inter- and intraindividual variations. The interdigitated microelectrode sensor system was used to measure plasma Aβ levels on a scale of 0.1 pg/ml. The implementation of this self-standard blood test resulted in substantial distinctions between patients with AD and individuals with normal cognition (NC), with selectivity and sensitivity over 90%.
检测淀粉样蛋白-β (Aβ) 聚集体有助于阿尔茨海默病 (AD) 的诊断。血浆 Aβ 被认为是 AD 的一种侵袭性较小且更容易获得的标志物，因为 Aβ 可以穿透血脑屏障。然而，生物流体 Aβ 浓度与 AD 进展之间的相关性一直很微弱。在这里，我们引入了一种诊断技术，该技术比较了血浆中 Aβ 的异质态和单体态。我们使用了一种小分子 EPPS [4-(2-羟乙基)-1-哌嗪丙磺酸] 将聚集的 Aβ 解离成单体，以提高定量准确性。随后，将 EPPS 处理后的血浆 Aβ 水平与未经处理的样品进行比较，以最大程度地减少个体间和个体内的差异。交错微电极传感器系统用于测量 0.1 pg/ml 范围内的血浆 Aβ 水平。实施这种自我标准化的血液测试，使得 AD 患者与认知正常 (NC) 个体之间存在显著差异，其选择性和灵敏度超过 90%。
