This review summarizes recent advancements in mouse models of Alzheimer's disease (AD), focusing on their phenotypes, advantages, limitations, and molecular signatures. Alzheimer's disease is the most common neurodegenerative disorder in the US, characterized by memory loss, confusion, and behavioral changes. Despite promising results from anti-amyloid therapies, more effective treatments are needed. Key AD pathologies include amyloid plaques and neurofibrillary tangles (NFTs), with risk factors such as APOE4 and TREM2. Mouse models, particularly transgenic (Tg) models, have been developed to study AD mechanisms and test therapies. However, newer models using knock-in (KI)/knock-out (KO) or CRISPR technologies aim to more accurately model AD without overexpression of human AD genes. Commonly used Tg models include Tg2576, TgCRND8, APP/PS1, 5xFAD, and 3xTg-AD, while new KI/KO models include APP-KI, Tau-KI, and TREM2-KO. These models exhibit varying degrees of amyloid and tau pathology, synaptic and neuronal degeneration, and cognitive deficits. Molecular data from these models have been analyzed to identify signatures resembling human AD brain changes, aiding in the selection of appropriate models for specific research questions. Tg2576 mice show early amyloid accumulation and cognitive deficits, with sex-specific differences. TgCRND8 mice develop amyloid plaques and cognitive impairments, with metabolic disturbances. Tau models like PS19 and rTg4510 exhibit tau pathology but lack amyloid pathology. The 5xFAD model is widely used for amyloid pathology and cognitive deficits, while the 3xTg model develops both amyloid and tau pathology. KI models like APP-KI and MAPT-KI offer more accurate human tau pathology but lack NFTs. These models have varying degrees of neuroinflammation, neuronal loss, and behavioral deficits, with sex-specific differences. Overall, these models provide valuable tools for studying AD mechanisms and testing therapies, but challenges remain in accurately modeling human AD pathology.This review summarizes recent advancements in mouse models of Alzheimer's disease (AD), focusing on their phenotypes, advantages, limitations, and molecular signatures. Alzheimer's disease is the most common neurodegenerative disorder in the US, characterized by memory loss, confusion, and behavioral changes. Despite promising results from anti-amyloid therapies, more effective treatments are needed. Key AD pathologies include amyloid plaques and neurofibrillary tangles (NFTs), with risk factors such as APOE4 and TREM2. Mouse models, particularly transgenic (Tg) models, have been developed to study AD mechanisms and test therapies. However, newer models using knock-in (KI)/knock-out (KO) or CRISPR technologies aim to more accurately model AD without overexpression of human AD genes. Commonly used Tg models include Tg2576, TgCRND8, APP/PS1, 5xFAD, and 3xTg-AD, while new KI/KO models include APP-KI, Tau-KI, and TREM2-KO. These models exhibit varying degrees of amyloid and tau pathology, synaptic and neuronal degeneration, and cognitive deficits. Molecular data from these models have been analyzed to identify signatures resembling human AD brain changes, aiding in the selection of appropriate models for specific research questions. Tg2576 mice show early amyloid accumulation and cognitive deficits, with sex-specific differences. TgCRND8 mice develop amyloid plaques and cognitive impairments, with metabolic disturbances. Tau models like PS19 and rTg4510 exhibit tau pathology but lack amyloid pathology. The 5xFAD model is widely used for amyloid pathology and cognitive deficits, while the 3xTg model develops both amyloid and tau pathology. KI models like APP-KI and MAPT-KI offer more accurate human tau pathology but lack NFTs. These models have varying degrees of neuroinflammation, neuronal loss, and behavioral deficits, with sex-specific differences. Overall, these models provide valuable tools for studying AD mechanisms and testing therapies, but challenges remain in accurately modeling human AD pathology.