Alzheimer’s disease (AD) is a progressive and fatal neurodegenerative disorder. The aggregation of hyperphosphorylated tau into neurofibrillary tangles (NFT) is a hallmark in the histopathology of AD. A number of mouse models have been created to study the major neuropathological mechanism and the research on drugs. We provide here some considerations for selecting a mouse model of AD, including tau transgenic mice, hyperphosphorylated tau animal model iduced by imbalance of the activities of kinases and phosphatases, hyperphosphorylated tau animal model induced by decreasing O-GlcNAcylation.