CREB1 and Alzheimer disease: Insulin-like growth factor-2 (IGF-2) was reported to attenuate memory decline and amyloid plaque formation in AD mouse model by activating the PI3K/AKT/CREB signaling pathway (Xia et al., 2019), and insulin has been observed to promote neuron growth and synapse formation through the PI3K signaling pathway (Liem et al., 2017; Gabbouj et al., 2019).