APOE and Alzheimer disease: Based on our previous finding that ApoE4 affects expression of SirT1 by binding to the SirT1 gene promoter20 - acting as transcriptional ‘brake’ on SirT1 expression - and that lower SirT1 levels are implicated in AD21, we sought to identify a SirT1 enhancer that was efficacious in the presence of ApoE4 as a potential novel therapeutic for AD.