The 3xTg-AD mouse model though faithfully reproduces characteristic features of AD, i.e., cognitive impairment and neurodegeneration associated with Aβ plaques and neurofibrillary pathology of hyperphosphorylated tau, the underlying disease mechanism in this triple-transgenic model which incorporates two APP and one presenilin-1 AD and one tau frontotemporal dementia mutations is probably very different from human AD. This evidence concerns the gene APP and Alzheimer disease.