SIRT1 and Alzheimer disease: The disease spectrum was separated back into four distinct groups to enforce monotonic directionality of gene expression changes in an expected direction of upregulation (control < hippocampal sparing AD < typical AD < limbic predominant AD) as exampled by SIRT1 or downregulation (limbic predominant AD < typical AD < hippocampal sparing AD < control) as exampled by PSEN2 (Fig. 3f, g and Supplementary Fig. 2).