In our previous research, we showed that melatonin mitigated the AD-related pathology in a hybrid icvAβ1-42 + pin model by stimulating the non-amyloidogenic pathway through both non-receptor mechanisms (SIRT1) and receptor-mediated ERK1/2/CREB signaling in the hippocampus [46]. Here, CREB1 is linked to Alzheimer disease.