PRNP and Alzheimer disease: Here, we utilize a homozygous double knock-in (DKI) mouse model with expression from the endogenous App and Mapt loci (AppNL−G−F/NL−G−F, MapthMAPT/hMAPT [19, 24, 25] to investigate the effects of constitutive Prnp loss on AD-related phenotypes.