Learning and memory deficits in a novel mouse model of Alzheimer's disease

Alzheimer's disease (AD) is responsible for major financial and health‐care burdens to society, burdens that are likely to grow as our population ages. Decades of research have associated the development of AD with the production of toxic forms of the Aβ peptide, through proteolysis of the Amyloid Precursor Protein (APP), that contribute to the development of brain plaques. Traditional mouse models of AD use massive overexpression of APP. This approach has produced many therapeutics that are effective in animal models but has not resulted in notable clinical success, likely because of the nonspecific effects of APP overexpression. Moreover, this process of generating plaques is very distinct from the processes seen in human AD patients. Therefore, in the present study we evaluated the learning and memory in a state‐of‐the‐art triple knock‐in mouse model of AD. We assessed learning and memory using a variety of behavioral tasks and we have established the time‐course of the progression of learning and memory deficits in this novel model of AD. Moreover, we found clear differences between male and female mice from this genetic lineage, a finding of interest as AD disproportionately affects women. If future studies, we will use sophisticated and sensitive operant techniques to further characterize the deficits observed in this new mouse model of AD.