PSEN1 and Alzheimer disease: However, two other pathways of the UPR (i.e., ATF6 and IRE1α) are not activated in APP/PS1 or prion-diseased mice (Ma et al., 2013; Moreno et al., 2013), and it currently remains unclear whether PERK overactivation found in AD animal models may be part of the UPR signaling (Endres and Reinhardt, 2013).