Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience , National Center for Nanoscience and Technology , 11 Beiyitiao , Haidian District, Beijing 100190 , China.
University of Chinese Academy of Sciences , 19 A Yuquan Road , Shijingshan District, Beijing 100049 , China.
ACS Appl Mater Interfaces. 2020 Feb 26;12(8):9693-9700. doi: 10.1021/acsami.0c00370. Epub 2020 Feb 12.
Alzheimer's disease (AD) is the most common neurodegenerative disorder with a continuous pathophysiological process starting from the preclinical and mild cognitive impairment (MCI) phases to the dementia phase. Early diagnosis is prerequisite for the early intervention of AD but meanwhile challenging. Amyloid-beta 1-42 (Aβ) plays a crucial part in AD pathology. Positron-emission tomography (PET) imaging of Aβ in the brain and the measurement of Aβ in the cerebrospinal fluid (CSF) have been adopted for the auxiliary diagnosis of AD, but their widespread clinical application has been limited due to the radiation and the high-cost of PET and the invasive lumbar puncture for collecting CSF. Noninvasive and cost-effective blood-based assay is desirable for the early diagnosis of AD. Here, a label-free assay for the quantification of blood Aβ was developed using the high-throughput surface plasmon resonance imaging method with the aid of an antibody-mimetic peptoid nanosheet equipping Aβ-recognizing loops. We demonstrated that this nanosheet-based sensor system could distinguish the plasma and sera from normal individuals and patients suffering AD and amnestic MCI with high sensitivity and specificity, preceding the diagnostic performance of the Aβ-recognizing molecule and the antibody specific to Aβ. This work provides a label-free, cost-effective, highly sensitive, and high-throughput blood-based assay for early detection of AD.
阿尔茨海默病（AD）是最常见的神经退行性疾病，具有连续的病理生理过程，从临床前和轻度认知障碍（MCI）阶段到痴呆阶段。早期诊断是 AD 早期干预的前提，但同时具有挑战性。β淀粉样蛋白 1-42（Aβ）在 AD 病理学中起着至关重要的作用。脑内 Aβ的正电子发射断层扫描（PET）成像和脑脊液（CSF）中 Aβ的测量已被用于 AD 的辅助诊断，但由于 PET 具有放射性且成本高，以及采集 CSF 时需要进行有创腰椎穿刺，其广泛的临床应用受到限制。对于 AD 的早期诊断，需要一种非侵入性且具有成本效益的基于血液的检测方法。在这里，我们使用高通量表面等离子体共振成像方法，借助具有 Aβ识别环的抗体模拟肽纳米片，开发了一种用于定量检测血液 Aβ 的无标记检测方法。我们证明，这种基于纳米片的传感器系统能够以高灵敏度和特异性区分来自正常个体和 AD 及遗忘性 MCI 患者的血浆和血清，其诊断性能优于 Aβ 识别分子和针对 Aβ 的抗体。这项工作为 AD 的早期检测提供了一种无标记、经济高效、高灵敏度和高通量的基于血液的检测方法。
