Bioluminescence imaging of Aβ deposition in bigenic mouse models of Alzheimer's disease
- 24 January 2011
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 108 (6), 2528-2533
- https://doi.org/10.1073/pnas.1019034108
Abstract
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.Keywords
This publication has 38 references indexed in Scilit:
- Live imaging of amyotrophic lateral sclerosis pathogenesis: Disease onset is characterized by marked induction of GFAP in Schwann cellsGlia, 2008
- Rapid appearance and local toxicity of amyloid-β plaques in a mouse model of Alzheimer’s diseaseNature, 2008
- Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse ModelNeuron, 2007
- Two-day radial-arm water maze learning and memory task; robust resolution of amyloid-related memory deficits in transgenic miceNature Protocols, 2006
- Neuronal α-Synucleinopathy with Severe Movement Disorder in Mice Expressing A53T Human α-SynucleinNeuron, 2002
- Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivoNature, 2002
- Early-onset Amyloid Deposition and Cognitive Deficits in Transgenic Mice Expressing a Double Mutant Form of Amyloid Precursor Protein 695Journal of Biological Chemistry, 2001
- Strain and gender differences in the behavior of mouse lines commonly used in transgenic studiesPhysiology & Behavior, 2001
- Aβ peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's diseaseNature, 2000
- High-Level Neuronal Expression of Aβ1–42in Wild-Type Human Amyloid Protein Precursor Transgenic Mice: Synaptotoxicity without Plaque FormationJournal of Neuroscience, 2000