Taken collectively, this is the first time that SCM-198 has been demonstrated to alleviate cognitive deficits in AβPP/PS1 mice.SCM-198 inhibits microglial overactivation, enhances CREB/BDNF-TrkB signaling and therefore promotes neuronal survival both in vitro and in vivo, suggesting that SCM-198 might become a promising candidate drug for AD therapy. Here, CREB1 is linked to Alzheimer disease.