Among the most upregulated genes in XO4+, microglia were the two most highly penetrant LOAD risk factor genes, the receptor Trem2 and its ligand Apoe28, as well as genes encoding their interacting partners, Tyrobp10 and Lpl, Ldlr, Lrpap1 (reviewed in29), respectively, suggesting a link between phagocytosis and cholesterol transport pathways and the XO4+ phenotype in AD. This evidence concerns the gene TREM2 and Alzheimer disease.