Since 2000, a plethora of transgenic mouse models have been developed to reproduce the main features of Alzheimer's disease (AD). Due to the complexity of the disease, no ideal animal model exists to date. The 5×FAD mouse line recapitulates numerous neuropathological insults and cognitive alterations found in human AD patients: from amyloid deposits to intense gliosis and neuroinflammation, including neurotransmission alteration, synaptic loss, neurodegeneration, and behavioral and memory deficits. The extremely aggressive amyloid pathology of these mice makes them a suitable model for early-onset AD. This chapter describes and illustrates the main characteristics of the 5×FAD mouse model and discusses its usefulness in the context of preclinical evaluation of drug candidates or promising therapeutic targets against AD.