Preclinical studies in Alzheimer’s disease (AD) are an active area that attracts many efforts in the search for useful drugs against this devastating neurodegenerative disease. The development of transgenic mice with familial AD genes has been pursued for more than 25 years, in an effort to model AD pathology. Some of the mouse models have proven useful in partially reproducing AD processes and are widely used for drug testing. Recently, novel AD mice bearing a humanized amyloid β sequence in the endogenous App gene may represent a major leap in moving toward reliable models. Nongenetically modified senescent mice have also sparked researchers’ interest to better model sporadic AD, as age is the main risk factor for AD. Methods to characterize mice phenotype are standardized and the required equipment is commercially available. The frontline tests are the effect of drugs against cognitive loss, the main concern of AD patients, and also against behavioral changes known as behavioral and psychological symptoms of dementia (BPSD). Responses of learning and memory are readily analyzed in a battery of tests of spatial and recognition memory. BPSD-like responses such as anxiety, exploration, and changes in social interaction can be tested in specific settings. A second line of tests is the analysis of brain tissue for changes in amyloid and tau AD pathology and associated neurodegenerative biomarkers, such as neuroinflammation, oxidative stress, and neuronal cell death. Next, other precise analyses can be performed according to specific mechanisms or by searching novel pharmacological targets and translational biomarkers.