Correlations between ApoE4 expression, SirT1 levels, and AD-related mechanisms have been seen in an animal model, including detection of a decrease in SirT1 mRNA in the frontal cortex of ApoE4 mice12 and altered expression of proteins that increase the activity of the β-secretase responsible for the first step in Aβ generation, BACE113. This evidence concerns the gene APOE and Alzheimer disease.