Open AccessBioluminescence imaging of Aβ deposition in bigenic mouse models of Alzheimer's disease
Author(s) -
Joel C. Watts,
Kurt Giles,
Sunny K. Grillo,
Azucena Lemus,
Stephen J. DeArmond,
Stanley B. Prusiner
Publication year - 2011
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1019034108
Subject(s) - bioluminescence imaging , luciferase , genetically modified mouse , bioluminescence , alzheimer's disease , pathology , transgene , biology , microbiology and biotechnology , medicine , disease , biochemistry , gene , transfection
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 theGfap 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.