Beta-amyloid (Aβ), the most pivotal pathological hallmark for Alzheimer's disease (AD) diagnosis and drug evaluation, was recognized by , a high-affinity fluorescent probe developed by rational molecular design. With a TICT mechanism, exhibited remarkable affinity with Aβ aggregates (K = 81.54 nM for oligomers; K = 66.70 nM for fibril) and substantial fluorescence enhancement (F/F = 44), enabling real-time monitoring of Aβ in live cells and nematodes. Significantly, this work used to construct a new protocol that can quickly and conveniently monitor Aβ changes at the cellular and nematode levels to evaluate the anti-AD efficacy of candidate compounds, and four reported Aβ-lowering drug candidates were administrated for validation. Imaging data demonstrated that can visually and quantitatively track the effect of Aβ elimination after drug treatment. Furthermore, excelled in histological staining of 12-month-old APP/PS1 mouse brains, accurately visualizing Aβ plaques. Integrating CUBIC technology, facilitated whole-brain, 3D imaging of Aβ distribution in APP/PS1 mice, enabling high-resolution analysis of Aβ plaques. Collectively, these innovative applications of offer a promising strategy for rapid, convenient, and real-time monitoring of Aβ levels in preclinical therapeutic assessments.

中文翻译：

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合理设计高亲和力荧光探针，用于可视化监测抗阿尔茨海默病候选药物的β淀粉样蛋白清除效果


β-淀粉样蛋白（Aβ）是阿尔茨海默病（AD）诊断和药物评价最关键的病理标志，它被一种通过合理分子设计开发的高亲和力荧光探针所识别。通过 TICT 机制，与 Aβ 聚集体表现出显着的亲和力（寡聚物的 K = 81.54 nM；原纤维的 K = 66.70 nM）和显着的荧光增强（F/F = 44），从而能够实时监测活细胞和线虫中的 Aβ 。值得注意的是，这项工作用于构建一个新的方案，可以快速、方便地监测细胞和线虫水平上的 Aβ 变化，以评估候选化合物的抗 AD 功效，并且对四种报告的降低 Aβ 的候选药物进行了验证。影像数据证明可以直观、定量地追踪药物治疗后Aβ消除的效果。此外，在 12 个月大的 APP/PS1 小鼠大脑的组织学染色方面表现出色，能够准确地显示 Aβ 斑块。集成 CUBIC 技术，促进了 APP/PS1 小鼠 Aβ 分布的全脑 3D 成像，从而实现了 Aβ 斑块的高分辨率分析。总的来说，这些创新应用为临床前治疗评估中快速、方便和实时监测 Aβ 水平提供了一种有前景的策略。