This review provides an overview of mouse models used in Alzheimer's disease (AD) research, focusing on both traditional transgenic (Tg) models and newer knock-in (KI)/knock-out (KO) models. The authors discuss the phenotypic characteristics of these models, including amyloid and tau pathology, synaptic and neuronal degeneration, and cognitive and behavioral deficits. They also highlight the advantages and limitations of each model, particularly in terms of sex-specific features. Additionally, the review analyzes omics data from various AD mouse models to categorize molecular signatures that resemble human AD brain changes, aiming to guide future model selection for specific research questions. The authors emphasize the need for developing novel model systems, such as chimeric models incorporating human induced pluripotent stem cells, to better capture the heterogeneity of AD and its underlying mechanisms.This review provides an overview of mouse models used in Alzheimer's disease (AD) research, focusing on both traditional transgenic (Tg) models and newer knock-in (KI)/knock-out (KO) models. The authors discuss the phenotypic characteristics of these models, including amyloid and tau pathology, synaptic and neuronal degeneration, and cognitive and behavioral deficits. They also highlight the advantages and limitations of each model, particularly in terms of sex-specific features. Additionally, the review analyzes omics data from various AD mouse models to categorize molecular signatures that resemble human AD brain changes, aiming to guide future model selection for specific research questions. The authors emphasize the need for developing novel model systems, such as chimeric models incorporating human induced pluripotent stem cells, to better capture the heterogeneity of AD and its underlying mechanisms.