Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 6, Pages 2528-2533Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1019034108
Keywords
optical imaging; prion-like transmission; seeding
Categories
Funding
- National Institutes of Health [R37 AG031220]
- Hillblom Foundation
- Canadian Institutes of Heath Research (CIHR)
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Transgenic (Tg) mouse models of Alzheimer's disease have served as valuable tools for investigating pathogenic mechanisms related to A beta 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 A beta 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 A beta 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 A beta 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 A beta-directed therapeutics.
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