APP-KI mice do not display the hallmark age-dependent cognitive decline of amyloid diseases

APP knock-in (KI) mice serve as an exciting new model system to understand amyloid beta (Aβ) pathology, overcoming many of the limitations of previous overexpression-based model systems. The APP SAA mouse model (containing the humanized APP with three familial Alzheimer’s disease mutations) and the APP WT control are the first commercially available APP KI mice within the United States. While APP SAA mice have been shown to develop progressive Aβ pathology and neuroinflammation, behavioral changes, particularly in cognitive functions, have yet to be described. Therefore, we performed an in-depth longitudinal study over 12 months, assessing cognition in these two strains, as well as assessments of motor and GI function. We surprisingly note no overt, progressive cognitive impairment or motor deficits. However, we do observe a significant increase in fecal output in APP SAA mice compared to APP WT at 12 months old. These data provide a baseline for these models’ behavioral attributes. Highlights APP SAA and APP WT knock-in mice do not display age related cognitive decline Fecal output appears altered by APP genotype, but no other measure of GI function is impacted. Both genotypes behave equally in motor function tests