Importantly, GLP-1R or GLP-1R/GIPR dual agonists were shown to enhance CREB activity in various non-pathologic or pathologic contexts in vitro (Velmurugan et al., 2012; Yang et al., 2016), in adult mice (Ohtake et al., 2014) as well as AD (Cai et al., 2018; Li et al., 2020a), PD (Jalewa et al., 2017; Zhang L.Y. et al., 2021), and T2DM (Gumuslu et al., 2016) animal models in vivo. This evidence concerns the gene CREB1 and Alzheimer disease.