Finally, a small but exceptionally tightly correlated metagene, called Inflame (Fig. 3), contained about 250 genes upregulated with AD, including many inflammation markers, such as IL1B, IL10, IL16, IL18, and HLA genes, as well as markers of macrophages, such as VSIG4, SLC11A1, and apoptosis, such as CASP1/4, TNFRSF1B (p75 death receptor) (Table 2, S2, Fig. S4). Inflame score explained 11% of variance in differentially expressed genes and positively correlated with BioAge (ρ = 0.47, p = 1E–10) and chronological age (ρ = 0.28, p<0.001) in AD samples. When used as a classifier, the Inflame score was capable of discriminating AD and normal brain with AUROC of 0.69. These genes maintained their mutual correlation in both normal and AD samples but reached significantly higher levels in AD (Table 1).
