APP and Alzheimer disease: Analysis of transgenic APP models, which are extensively used in AD research, are confounded by several factors: the overexpression of APP above physiological levels (Saito et al., 2016), the disruption of genes in the transgene integration sites (Goodwin et al., 2019; Tosh et al., 2017), the use of exogenous promoters, which do not replicate the temporal, cell type-specific or spatial expression of the endogenous gene (Rodgers et al., 2012), and the overproduction of multiple, biologically active APP metabolites.