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量子点探针与抗 Aβ抗体偶联用于阿尔茨海默病小鼠模型的分子成像。

A quantum dot probe conjugated with aβ antibody for molecular imaging of Alzheimer's disease in a mouse model.

机构信息

Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.

出版信息

Cell Mol Neurobiol. 2013 Aug;33(6):759-65. doi: 10.1007/s10571-013-9943-6. Epub 2013 May 22.

Abstract

The treatment of Alzheimer's disease (AD) has been hampered by a lack of sensitive and specific non-invasive diagnostic methods. Quantum dots (QD) are nano-crystals with unique photo-physical properties that bypass some of the limitations of conventional dyes and imaging tools. This study is aimed to evaluate the fluorescence properties of a QD probe conjugated with an anti-Aβ antibody (QD-Aβ-Ab). Healthy mice and mice bearing mutated human APP695swe and APP717 V-F transgenes received intracerebroventricular injection of the probe for subsequent imaging. Immunohistochemistry revealed that Aβ1-42 was distributed in the hippocampus CA1 area in the APP transgenic mice. Fluorescence microscopy demonstrated that fluorescence was mainly observed in the hippocampus area, the cerebral cortex, sagittal septum and striatum of APP transgenic mice. In vivo imaging of mice receiving the QD-Aβ-Ab probe showed that healthy mice exhibited a narrow range of fluorescence and lower fluorescence intensity compared with APP transgenic mice. The mean fluorescence intensity of brain tissues of healthy C57BL mice was 12.3784 ± 3.9826, which was significantly lower than that of 10- and 16-month-old APP transgenic mice (45.03 ± 2.66 and 46.69 ± 3.22, respectively; P < 0.05). In this study we present the first direct evidence that QD-Aβ-Ab conjugate probes can track in vivo state of Aβ accumulation in mice and the findings suggest that such probes may be of potential use for early molecular diagnostic imaging of AD.

摘要

阿尔茨海默病(AD)的治疗受到缺乏敏感和特异性的非侵入性诊断方法的阻碍。量子点(QD)是具有独特光物理特性的纳米晶体,可绕过传统染料和成像工具的一些限制。本研究旨在评估与抗 Aβ 抗体(QD-Aβ-Ab)偶联的 QD 探针的荧光特性。健康小鼠和携带突变人类 APP695swe 和 APP717 V-F 转基因的小鼠接受脑室内注射探针,随后进行成像。免疫组织化学显示 Aβ1-42 分布在 APP 转基因小鼠的海马 CA1 区。荧光显微镜显示荧光主要观察到在 APP 转基因小鼠的海马区、大脑皮层、矢状隔和纹状体。接受 QD-Aβ-Ab 探针的小鼠体内成像显示,与 APP 转基因小鼠相比,健康小鼠表现出荧光范围较窄且荧光强度较低。健康 C57BL 小鼠脑组织的平均荧光强度为 12.3784 ± 3.9826,明显低于 10 月龄和 16 月龄 APP 转基因小鼠(分别为 45.03 ± 2.66 和 46.69 ± 3.22;P < 0.05)。本研究首次直接证明 QD-Aβ-Ab 缀合物探针可以在体内追踪 Aβ 积累的状态,研究结果表明,这些探针可能对 AD 的早期分子诊断成像具有潜在的应用价值。

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