We also demonstrate the in vitro and in vivo efficacy of our brain-permeable SirT1 enhancer lead candidate DDL-218, which significantly increased SirT1 mRNA in both N2a-E4 and human Kelly neuroblastoma cells, and in hippocampus/entorhinal cortex of ApoE4-TR:5xFAD mice after 56-day treatment at 40 mg/kg/day. This evidence concerns the gene SIRT1 and neuroblastoma.