APP and Alzheimer disease: The Ts65Dn mice at that age do not exhibit increased levels of APP in the hippocampus [45] and lack the insoluble amyloid plaques and neurofibrillary tangles characteristic of AD [15,46], but do show some early symptoms of AD-related pathologies such as increased levels of soluble amyloid Aß40 and Aß42 in the hippocampus [47], signs of hippocampal-dependent cognitive impairments [46,48], and hippocampal degeneration [49].