SIRT1 and Alzheimer disease: These data, taken together with multiple lines of evidence for a paradoxical up-regulation of synaptic elements within the frontal cortex during MCI (Counts et al., 2006; Bell et al., 2007; Williams et al., 2009; Bossers et al., 2010), suggest that sirt1 may mediate a synaptic remodeling response to mounting pathology during the progression of AD.