This model shows that SIRT6 is the only sirtuin that is downregulated at a relatively early age, and it may be related to global acetylation of histone H3 as well as other epigenetic abnormalities found in the AD brain (Kanfi et al., 2012; Grinan-Ferre et al., 2016). The gene discussed is SIRT6; the disease is Alzheimer disease.