Bioluminescence imaging of Abeta deposition in bigenic mouse models of Alzheimer's disease.
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.
Department of Neurology and Pathology, Institute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143, USA.
Joel C
JC
Watts
Kurt
K
Giles
Sunny K
SK
Grillo
Azucena
A
Lemus
Stephen J
SJ
DeArmond
Stanley B
SB
Prusiner
D000375:Aging / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D003952:Diagnostic Imaging; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D049449:Luminescence; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics
C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; C528900:glial fibrillary astrocytic protein, mouse; D008156:Luciferases
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