Higher BioAge of AD patients explained more than 50% of the differential expression between normal and AD cohorts. In the range of BioAge scores in which AD and normal individuals overlap, there was a significant residual differential expression, composed of several distinct subpatterns that explain a large fraction of the normal-to-AD variance. We focused on 88 AD and 43 normal brain samples with matched moderate levels of BioAge between −0.1 and 0.3. We identified 625 genes that are differentially expressed between the two cohorts (ANOVA p<0.005, absolute fold change >25%, FDR<0.1). Figure 3A shows the supervised metagene analysis of these genes based on clustering using gene-gene correlation as a distance measure (see Methods). In this analysis we identified the 3 most regulated metagenes responsible for the majority of the gene expression differences associated with the disease.
