PSEN1 and Alzheimer disease: Recently, a study showed that verteporfin only bound with the APP transmembrane domain rather than the transmembrane domain of the Notch-1 receptor, indicating its inhibitory effect is in a C99-specific manner.437 Our study also showed that PSEN1S169del (a deletion mutation in PSEN1 gene exon 6) has distinct effects on APP processing and Notch1 cleavage.39 This AD pathogenic mutation altered APP processing and Aβ generation without affecting Notch-1 cleavage and Notch signaling in vitro and in vivo.