Characterization of learning deficits in two models of Alzheimer's disease

Mouse models of Alzheimer's disease provide a powerful tool for studying mechanisms and treatments of neurological disease. Thorough analyses of these models, behaviour provides a means to assess whether therapeutic interventions designed to alter disease process will affect disease manifestation. In this study, we undertake a detailed analysis of phenotype progression in two lines of Alzheimer's mice, the 5XFAD line, which carries the human APP(695) with the Swedish (K670N, M671L), Florida (I716V), and London (V717I) Familial Alzheimer's Disease (FAD) mutations and human PS1 harboring two FAD mutations, and J20 line, which carries the human amyloid protein precursor bearing both the Swedish (K670N/M671L) and the Indiana (V717F) mutation. We study the progression of the learning deficit in radial arm maze, fear conditioning and Y-maze, and we assess progression of anxiety phenotype in elevated plus maze and open field. We also assess neuro-anatomical correlates of the learning deficits. A thorough knowledge of phenotype progression in these models will assist in future studies directed to determine an optimal strategy for testing therapeutic intervention's.