Department of Neurology and Pathology, Institute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143, USA.
Proc Natl Acad Sci U S A. 2011 Feb 8;108(6):2528-33. doi: 10.1073/pnas.1019034108. Epub 2011 Jan 24.
Transgenic (Tg) mouse models of Alzheimer's disease have served as valuable tools for investigating pathogenic mechanisms related to Aβ accumulation. However, assessing disease status in these animals has required time-consuming behavioral assessments or postmortem neuropathological analysis. Here, we report a method for tracking the progression of Aβ accumulation in vivo using bioluminescence imaging (BLI) on two lines of Tg mice, which express luciferase (luc) under control of the Gfap promoter as well as mutant human amyloid precursor protein. Bigenic mice exhibited an age-dependent increase in BLI signals that correlated with the deposition of Aβ in the brain. Bioluminescence signals began to increase in 7-mo-old Tg(CRND8:Gfap-luc) mice and 14-mo-old Tg(APP23:Gfap-luc) mice. When Tg(APP23:Gfap-luc) mice were inoculated with brain homogenates from aged Tg(APP23) mice, BLI detected the accelerated disease onset and induced Aβ deposition at 11 mo of age. Because of its rapid, noninvasive, and quantitative format, BLI permits the objective repeated analysis of individual mice at multiple time points, which is likely to facilitate the testing of Aβ-directed therapeutics.
阿尔茨海默病的转基因 (Tg) 小鼠模型已成为研究与 Aβ 积累相关的致病机制的有价值的工具。然而，评估这些动物的疾病状态需要耗时的行为评估或死后神经病理学分析。在这里，我们报告了一种使用生物发光成像 (BLI) 跟踪两种 Tg 小鼠体内 Aβ 积累进展的方法，这两种小鼠的 luc 在 Gfap 启动子的控制下表达，以及突变的人类淀粉样前体蛋白。双基因小鼠表现出与大脑中 Aβ 沉积相关的年龄依赖性 BLI 信号增加。7 月龄的 Tg(CRND8:Gfap-luc) 小鼠和 14 月龄的 Tg(APP23:Gfap-luc) 小鼠开始增加生物发光信号。当 Tg(APP23:Gfap-luc) 小鼠接种来自老年 Tg(APP23) 小鼠的脑匀浆时，BLI 在 11 月龄时检测到疾病的加速发作并诱导 Aβ 沉积。由于其快速、非侵入性和定量的格式，BLI 允许在多个时间点对单个小鼠进行客观的重复分析，这可能有助于测试 Aβ 靶向治疗药物。
