Saura et al. showed that the deletion of presenilin1/2 reduced CBP levels, which decreased the transcription of CREB/CBP target genes such as c-fos and BDNF.168 A triple-transgenic model of AD (3xTg-AD) harboring three mutant genes (APP, PSEN1, and tau) shows plaque and tangle pathologies, and synaptic dysfunction and impaired neurogenesis.169,170 CREB activation and phosphorylation are impaired in the 3xTg-AD mice. Here, APP is linked to Alzheimer disease.