Modeling Alzheimer’s disease (AD) in vivo is a major challenge in neuroscience. Since the 1990s, multiple transgenic mouse models have been generated, providing key insights into amyloid-β (Aβ) pathology and therapeutic strategies. However, most rely on APP or APP/presenilin-1 (PS1) overexpression, which can produce artifacts related to protein overproduction or mislocalization. To overcome these drawbacks, single App knock-in lines carrying familial AD mutations have been developed. Here, we characterized behavioral and neuropathological traits of the new AppNL-F;Psen1P117L knock-in (APP KI) mouse strain. Homozygous APP KI and C57BL/6 wild-type (WT) mice were tested at 3 and 6 months in the open field, elevated plus maze, novel object recognition, and Y-maze tasks to evaluate locomotion, anxiety-like behavior, episodic memory, and working/spatial memory. At six months, APP KI mice exhibited preserved locomotor activity but increased novel arm entries with reduced exploration time, suggesting novelty-seeking/impulsivity and impaired sustained exploration. These changes correlated with moderate cortical Aβ deposition and minimal hippocampal pathology. Ongoing studies aim to expand this profile. Together, our findings strengthen the link between incipient neuropathology and early behavioral alterations in this new-generation AD model, providing measurable features relevant for testing disease-modifying interventions.