P2-388: Behavioral, biochemical and imaging characterization of an Alzheimer's disease CVN mouse

CVN mouse, with APPSweDI mutations and crossed with NOS2 knockout line, exhibits wide range of AD hallmarks including increased insoluble Aβ and plaque formation, inflammation, tau phosphorylation, hippocampal neuronal death and behavioral deficits (Wilcock et al 2008). Validation data from Charles River CVN mouse in-house testing colony shows reproducible AD defects, and positions CVN mouse as the most complete AD model available. Wild-type and CVN mice were studied starting at age of 3 months. Behavioral battery included Open field, Barnes maze, Radial arm water maze, and Contextual fear conditioning. At 3,6,9 and 12 months of age, tissue were collected for biochemical analysis. Immunohistochemical stainings for Aβ1–40 and microglia were performed, and neuronal number was evaluated by CFV histological staining. MRI volumetric as well as spectroscopic (1H-MRS) analyses were performed. CVN mice exhibited significant age-dependent behavioral deficits in Barnes maze, Radial arm water maze and Contextual fear conditioning. Robust biochemical changes, including increased number of dense amyloid plaques in hippocampus, thalamus and cortex, and increased levels of insoluble Aβ subtypes were evident. Significant inflammatory response detected by Iba-1 and CD45 immunoreactive microglia was heavily condensed around the plaques in all brain regions studied. The number of viable neurons in hippocampus was significantly decreased in aged animals. In 1H-MRS several translational AD-related metabolic changes were detected. The new CVN mouse provides a more complete tool to study novel therapies targeted for treatment of AD. Several desired AD-related end-points are present in this mouse line making it a valuable model for drug development.