Fig. 1

APOE2 single-nucleus profiling and pathway-level alterations. a Detailed information of APOE carriers from The Religious Orders Study and Memory and Aging Project (ROSMAP) (Created with https://www.biorender.com). b The UMAP plot displayed six main cell types in DLPFC. Ex: excitatory neurons; In: inhibitory neurons; Oli: oligodendrocytes; OPC: oligodendrocyte precursor cells; Ast: astrocytes; Mic: microglia. c Heatmap showed the expression of representative marker genes in each cell type. d Heatmap showed top Gene Ontology biological processes with expression changes associated with APOE2 (nominal P < 0.05, linear model, APOE32/3 versus APOE3/3), with red indicating APOE2 upregulation and blue indicating APOE2 downregulation. The color scale represented sign (log [FC]) × log10[P] values. e The curation process of mitochondrion-associated pathways, GO_BP, GO_Biological_Process_2021 database; KEGG, KEGG_2021_Human database; Reactome: Reactome_2022 database; HumanCyc: HumanCyc_2016 database. f Heatmap showed mitochondrion-associated pathways altered across major six cell types in APOE2 versus APOE3 individual (nominal P < 0.05, linear model). Red indicated APOE2 upregulation and blue indicated APOE2 downregulation. The color scale represents sign (log [FC]) × log10[P] values. Pathways with absolute value of sign (log [FC]) × log10[P] > 1.3 were shown in the heatmap