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用 [18F]AV-45 在 APP/PS1-21 小鼠淀粉样斑块沉积模型中进行 PET 成像。

PET imaging with [18F]AV-45 in an APP/PS1-21 murine model of amyloid plaque deposition.

机构信息

CEA/DSV/I2BM UMR 6301 ISTCT LDM-TEP, Université de Caen Basse-Normandie, Centre Cyceron, Caen, France.

出版信息

Neurobiol Aging. 2012 Nov;33(11):2561-71. doi: 10.1016/j.neurobiolaging.2011.12.024. Epub 2012 Jan 24.

Abstract

Alzheimer's disease (AD), the most common age-related neurodegenerative disorder, is characterized by the accumulation of β-amyloid peptide. In man, [18F]AV-45 with positron emission tomography (PET) is currently studied and used to track in vivo amyloid accumulation. Here, [18F]-AV45-PET was used to visualize amyloid deposition in a transgenic murine model of amyloidosis (APP/PS1-21). Studies were performed ex vivo by autoradiography and in vivo by microPET. Autoradiograms of the brain sections highlighted an increased uptake of [18F]AV-45 in APP/PS1-21 mice compared with age-matched control mice. From 8 months, an intense labeling was observed in cortex, hippocampus, and striatum. The marked accumulation of radiotracer was found in close association with thioflavin S-positive amyloid plaques. The longitudinal microPET assessment, performed from 3 to 12 months of age, demonstrated an increased [18F]AV-45 uptake in APP/PS1-21 compared with control mice. The elevated tracer uptake was increased in association with age. This study opens the possibility of [18F]AV-45, coupled with microPET, to visualize and quantitatively measure amyloid deposits in the brains of living APP/PS1 mice.

摘要

阿尔茨海默病(AD)是最常见的与年龄相关的神经退行性疾病,其特征是β-淀粉样肽的积累。在人类中,[18F]AV-45 正与正电子发射断层扫描(PET)一起被研究和用于追踪体内淀粉样蛋白的积累。在这里,[18F]-AV45-PET 被用于可视化淀粉样变性(APP/PS1-21)转基因小鼠模型中的淀粉样蛋白沉积。通过放射自显影术进行离体研究,通过 microPET 进行体内研究。脑切片的放射自显影图突出显示,与年龄匹配的对照小鼠相比,APP/PS1-21 小鼠中[18F]AV-45 的摄取增加。从 8 个月起,在皮质、海马体和纹状体中观察到强烈的标记。放射性示踪剂的明显积累与硫黄素 S 阳性淀粉样斑块密切相关。从 3 到 12 个月龄进行的纵向 microPET 评估表明,与对照小鼠相比,APP/PS1-21 小鼠中[18F]AV-45 的摄取增加。与年龄相关的升高的示踪剂摄取增加。这项研究为[18F]AV-45 与 microPET 结合使用提供了可能性,可用于可视化和定量测量活体 APP/PS1 小鼠大脑中的淀粉样沉积物。

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