APP and Alzheimer disease: Thus, many studies using genetic or pharmacological approaches to increase C99 levels in animal models consistently demonstrate the pathogenic properties of C99 linked with AD phenotypes (Neve et al., 1996; Oster-Granite et al., 1996; Song et al., 1998; Matsumoto et al., 2002; Lauritzen et al., 2012, 2016; Bourgeois et al., 2018).