Bioluminescence imaging of Ap deposition in bigenic mouse models of Alzheimer's disease

摘要

Transgenic (Tg) mouse models of Alzheimer's disease have served as valuable tools for investigating pathogenic mechanisms related to Ap 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 Ap accumulation in vivo using bio-luminescence imaging (BLI) on two lines of Tg mice, which express luciferase (Iuc) 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:G/ap-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 Ap 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 Ap-directed therapeutics.