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 (A{beta}) pathology, overcoming many of the limitations of previous overexpression-based model systems. The APPSAA mouse model (containing the humanized APP with three familial Alzheimers disease mutations) and the APPWT control are the first commercially available APP KI mice within the United States. While APPSAA mice have been shown to develop progressive A{beta} 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 APPSAA mice compared to APPWT at 12 months old. These data provide a baseline for these models behavioral attributes. HighlightsO_LIAPPSAA and APPWT knock-in mice do not display age related cognitive decline C_LIO_LIFecal output appears altered by APP genotype, but no other measure of GI function is impacted. C_LIO_LIBoth genotypes behave equally in motor function tests C_LI