Behavioral characterization of 5xFAD mice using standardized decision-making and open field assays

The 5xFAD mouse is a widely used transgenic model of Alzheimer’s disease (AD), characterized by early and aggressive amyloid-β plaque accumulation. However, the extent to which plaque burden in this model predicts functional impairment remains unclear, particularly during early to mid stages of pathology when substantial plaque deposition is already present. To further characterize behavior in this model using standardized assays, we systematically evaluated feedback-based associative learning, choice-switching behavior, and open field behavior in 5xFAD and wild-type mice (2–9 months of age) using the International Brain Laboratory decision-making task, a rigorously standardized behavioral paradigm, together with the commonly used open field test. Despite robust, age-dependent plaque accumulation, 5xFAD mice did not differ from age-matched controls in associative learning, choice-switching behavior, anxiety-like behavior, or locomotor activity. These results indicate that substantial amyloid plaque accumulation was not associated with measurable deficits in the behavioral domains examined during the early to mid stages of pathological progression. Our findings provide a standardized behavioral characterization of the 5xFAD model and highlight the need for more sensitive functional assays to further clarify the relationship between early amyloid pathology and behavioral outcomes in AD research.