Tg2576 Mouse Validation Data
The Tg2576 mouse model is used in Alzheimer’s disease research to test therapeutics targeting Alzheimer’s disease. Tg2576 mice overexpress a mutant form of amyloid precursor protein (APP), APPK670/671L, linked to early-onset familial Alzheimer’s disease (AD), developing amyloid plaques and progressive cognitive deficits. At Charles River, the Tg2576 transgenic mouse model has been validated using multiple endpoints including cognitive testing, measurement of the levels of soluble and insoluble beta amyloid, and biomarker measurement using immunohistochemical staining.
Our validation data indicates that the Tg2576 mouse shows impaired cognitive functions in the contextual fear conditioning test, coinciding with the increased cortical and hippocampal soluble beta amyloid levels, starting from 5 months of age. The increased insoluble beta amyloid levels and the amyloid plaques are evident at 13 months of age.
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Some study components include:
Behavioral Testing
- Contextual Fear Conditioning Test for cognitive deficits
- Touchscreen testing for cognitive deficits
- Open Field Test for motor changes
- Body weight changes
Biochemical Analysis
- Soluble Abeta 1-40 and Abeta1-42 levels in hippocampus, cortex, plasma and CSF
- Cytokine expression by ELISA
- IDE activity assay
- Phospho-GSK3beta assay
- Synaptophysin, C99, C83 and holoAPP WB
- Neurochemical profile by microdialysis (ACh, 5HT, NE, DA, Glu, metabolites)
- Tissue and Microdialysate samples for PK and/or Neurochemicals
Brain Pathology
- Astro- and Microgliosis by GFAP and Iba-1 immunohistochemical staining
- Cell proliferation by BrdU
- Plaque load in cortex and hippocampus at 9-12 months of age
Imaging
- T2-MRI for Cerebral Volumetry
- Proton Magnetic Resonance Spectroscopy (1H-MRS) for Hippocampal Metabolic Profile
- Arterial Spin Labeling MRI for cerebral blood flow at older ages
- Diffusion Tensor Imaging (DTI)
- Pharmacological MRI (phMRI)