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

Abstract

AbstractAPP 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 APPSAAmouse model (containing the humanized APP with three familial Alzheimer’s disease mutations) and the APPWTcontrol are the first commercially available APP KI mice within the United States. While APPSAAmice 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 APPSAAmice compared to APPWTat 12 months old. These data provide a baseline for these models’ behavioral attributes.HighlightsAPPSAAand APPWTknock-in mice do not display age related cognitive declineFecal output appears altered by APP genotype, but no other measure of GI function is impacted.Both genotypes behave equally in motor function tests