Alzheimer’s disease (AD) is characterized by progressive cognitive decline and memory loss. Animal models have been key to unraveling the molecular basis of AD pathology, yet behavioral characterization remains essential to link these alterations to functional outcomes. We have previously studied triple transgenic mice (3xTg-AD; PS1M146V, APPSwe, tauP301L; hybrid background) and reported memory impairments in novel object recognition, along with changes in amyloid aggregation and ERK1/2 signaling. Here we present an extended behavioral characterization of a novel congenic mouse line, 3xTg-C57, which combines the 3 transgenes with C57BL/6 genetic background. Male and female 3xTg-C57 and WT-C57 mice aged 4, 6, and 8 months were tested in tasks including open field, elevated plus maze (anxiety-like behavior), Y-maze (working memory), novel object recognition (episodic memory), and social preference/memory paradigms. In parallel, Congo red staining was applied to fixed-brain slices from the 3xTg-C57 and WT-C57 mice to assess β-amyloid deposition profiles, enabling the integration of brain histological characterization with behavioral features. By combining behavioral and histological analyses, this study aims to uncover sensitive functional outcomes of AD progression and improve the model’s translational utility.