Late disease also corresponded to a distinct microglial transcriptomic state in our RNAseq dataset, including apical expression of Apoe, B2m, Cd63, Fth1, Igf1, Lyz and Timp2. A key feature of late disease microglia was upregulation of the apolipoproteins Apoe, Apoc1 and Apoc4, suggesting altered lipid metabolism, which is a crucial factor for Alzheimer’s disease and reported to be associated to TREM2 signalling in microglia [36]. The gene discussed is APOC4; the disease is early-onset autosomal dominant Alzheimer disease.