Angiopep-2, an MRI Biomarker, Dynamically Monitors Amyloid Deposition in Early Alzheimer's Disease.
Angiopep-2, an MRI Biomarker, Dynamically Monitors Amyloid Deposition in Early Alzheimer's Disease.
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AngiOpep-2是MRI生物标志物，在早期阿尔茨海默氏病中动态监测淀粉样蛋白沉积。
DOI：
10.1021/acschemneuro.2c00513
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发表时间：
2023-01-18
影响因子：
5
通讯作者：
Wu, Renhua
中科院分区：
文献类型：
--
作者：
Xu, Liang;Lai, Lingfeng;Wen, Yaqi;Lin, Jia;Chen, Beibei;Zhong, Yazhi;Cheng, Yan;Zhang, XiaoLei;Guan, Jitian;Mikulis, David J.;Lin, Yan;Yan, Gen;Wu, Renhua
关键词：
使用成像技术可靠、动态地检测淀粉样蛋白 β 蛋白 (Aβ) 沉积对于临床前阿尔茨海默病 (AD) 是必要的，这可能会显着改善预后。本研究旨在评估应用 angiopep-2 (ANG)（一种化学交换饱和转移磁共振成像 (CEST-MRI) 生物标志物）监测体内 Aβ 沉积的可行性。 ANG 具有良好的化学交换饱和转移 (CEST) 效应，并在体外与 Aβ1-42 表现出中等的结合亲和力。注射 ANG 的 6 个月大 AD 小鼠在体内表现出比对照组显着增强的 CEST 效果；这种效果在第 8、10 和 12 个月时逐渐变得更加明显。 APPswe/PSEN1dE9（85 系）AD 小鼠在 12 个月时出现由大量 Aβ 沉积引起的空间学习障碍（代表 AD 患者的轻度认知障碍）。总之，ANG 的 CEST 可以显示 AD 小鼠中非常早期的与年龄相关的 Aβ 病理进展，这与免疫组织化学一致。 ANG 作为一种影像生物标志物具有巨大的临床转化潜力，可诊断早期 AD 并动态且非辐射地跟踪其进展。
The reliable and dynamic detection of amyloid β-protein (Aβ) deposition using imaging technology is necessary for preclinical Alzheimer’s disease (AD), which may significantly improve prognosis. The present study aimed to evaluate the feasibility of applying angiopep-2 (ANG), a chemical exchange saturation transfer-magnetic resonance imaging (CEST-MRI) biomarker, for monitoring Aβ deposition in vivo. ANG exerted a good chemical exchange saturation transfer (CEST) effect and displayed a moderate binding affinity to Aβ1–42 in vitro. Six-month-old mice with AD injected with ANG exhibited a significantly enhanced CEST effect than controls in vivo; this effect gradually became more apparent at 8, 10, and 12 months. Spatial learning impairment caused by abundant Aβ deposition (representing mild cognitive impairment in AD patients) develops at 12 months in APPswe/PSEN1dE9 (line 85) AD mice. To conclude, the CEST of ANG could display very earlier age-related Aβ pathological progress in mice with AD, consistent with immunohistochemistry. ANG has extraordinary potential for clinical transformation as an imaging biomarker to diagnose early AD and track its progress dynamically and nonradiationally.
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