<br>基于微阵列芯片的神经丝轻链自组装肽高通量筛选，用于阿尔茨海默病的无创监测,ACS Nano

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基于微阵列芯片的神经丝轻链自组装肽高通量筛选，用于阿尔茨海默病的无创监测
ACS Nano ( IF 15.8 ) Pub Date : 2024-06-28 , DOI: 10.1021/acsnano.3c09642
Ying Zhou _{1,

2} , Guoen Cai _{3,

4} , Yuanzhuo Wang _{2,

5} , Yuxin Guo ₂ , Zhimin Yang _{1,

2} , Anqi Wang _{1,

2} , Yongshou Chen ₆ , Xuejie Li _{1,

2} , Xiaochun Chen _{3,

4} , Zhiyuan Hu _{1,

2,

5,

6} , Zihua Wang _{1,

2}

Affiliation

阿尔茨海默病 (AD) 在认知症状出现前数十年就已开始。准确反映 AD 病理学的易于获取且具有成本效益的生物标志物对于 AD 的监测和治疗至关重要。 AD 患者血液和脑脊液中的神经丝轻链 (NfL) 水平在预期发病前十多年就增加，从而为 AD 监测提供了最有前途的血液生物标志物之一。在患者护理中常规使用单分子阵列（Simoa）技术的临床实践因成本高而受到限制。在此，我们开发了一种基于微阵列芯片的高通量筛选方法，并筛选了一种有吸引力的靶向NfL的自组装肽。通过直接“印迹”并进一步分析已识别的自组装肽的序列、形态和亲和力，Pep-NfL肽纳米片对NfL具有高结合亲和力（ K _D = 1.39 × 10 ^–9 mol/L），高具有特异性强、成本低的特点。 Pep-NfL 的卓越结合能力在 AD 小鼠模型和细胞系中得到证实。在临床环境中，Pep-NfL 肽纳米片在区分 AD 患者（ P < 0.001， n = 37）、轻度认知障碍患者（ P < 0.05， n = 26）和对照组（ n = 30）方面具有巨大潜力。）。这项工作为AD的无创追踪提供了一种高通量、高灵敏度和经济的系统，以监测疾病不同阶段的神经退行性变。获得的 Pep-NfL 肽纳米片可用于评估血浆 NfL 浓度的动态变化，以评估作为临床试验中神经退行性变的替代终点的疾病缓解疗法。

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Microarray Chip-Based High-Throughput Screening of Neurofilament Light Chain Self-Assembling Peptide for Noninvasive Monitoring of Alzheimer’s Disease

Alzheimer’s disease (AD) starts decades before cognitive symptoms develop. Easily accessible and cost-effective biomarkers that accurately reflect AD pathology are essential for both monitoring and therapeutics of AD. Neurofilament light chain (NfL) levels in blood and cerebrospinal fluid are increased in AD more than a decade before the expected onset, thus providing one of the most promising blood biomarkers for monitoring of AD. The clinical practice of employing single-molecule array (Simoa) technology for routine use in patient care is limited by the high costs. Herein, we developed a microarray chip-based high-throughput screening method and screened an attractive self-assembling peptide targeting NfL. Through directly “imprinting” and further analyzing the sequences, morphology, and affinity of the identified self-assembling peptides, the Pep-NfL peptide nanosheet with high binding affinity toward NfL (K_D = 1.39 × 10^–9 mol/L), high specificity, and low cost was characterized. The superior binding ability of Pep-NfL was confirmed in AD mouse models and cell lines. In the clinical setting, the Pep-NfL peptide nanosheets hold great potential for discriminating between patients with AD (P < 0.001, n = 37), mild cognitive impairment (P < 0.05, n = 26), and control groups (n = 30). This work provides a high-throughput, high-sensitivity, and economical system for noninvasive tracking of AD to monitor neurodegeneration at different stages of disease. The obtained Pep-NfL peptide nanosheet may be useful for assessing dynamic changes in plasma NfL concentrations to evaluate disease-modifying therapies as a surrogate end point of neurodegeneration in clinical trials.

更新日期：2024-06-28

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