Serum levels of SIRT1 decrease with age and more dramatically with MCI and AD diagnosis (Kumar et al., 2013) and SIRT1 mRNA levels have been shown to decrease in an ApoE−/− mouse model of AD together with loss of circadian rhythmicity compared to normal (C57BL/6J) mice (Zhou et al., 2016). Here, APOE is linked to Alzheimer disease.