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. Author manuscript; available in PMC: 2025 Apr 17.
Published in final edited form as: Neuron. 2024 Feb 9;112(8):1235–1248.e5. doi: 10.1016/j.neuron.2024.01.013

Figure 5. APOE genotype-dependent innate immune dysregulation in AD.

Figure 5.

(A) UpSet plot of AD vs. HC APOE genotype comparisons indicating increasing number of unique DARs by number of APOE ε4 alleles. Corresponding heatmap shows DARs by cell type for each APOE genotype comparison between AD and HC subjects. (B) Total number of overlapping DARs and DEGs by cell type for each APOE genotype comparison between AD and HC subjects indicating increasing number of genes in AD monocytes by number of APOE ε4 alleles. (C) Scatterplots showing DARs intersecting DEGs by fold change in CD14 monocytes for each AD vs. HC APOE genotype comparison. (D) Representative chromatin tracks of DARs intersecting DEGs in AD vs. HC APOE ε4/ε4 carriers. For each gene, significant DARs are shown in grey. (E) Transcription factor motif analysis in monocytes indicating enrichment of inflammatory transcription factors in AD APOE ε4/ε4 carriers, where transcription factors are ranked by product of log(p-value) and log2(fold-change). Group sizes for all comparisons: n = 9 HC APOE ε3/ε3, 10 HC APOE ε3/ε4, 7 HC APOE ε4/ε4, 10 AD APOE ε3/ε3, 11 AD APOE ε3/ε4, 8 AD APOE ε4/ε4. ATAC-seq assay: HC APOE ε3/ε3 monocytes = 2647, median (IQR) = 227.5 (135.75 – 542.5), HC APOE ε3/ε4 monocytes = 3436, median (IQR) = 275 (250 – 410), HC APOE ε4/ε4 monocytes = 3680, median (IQR) = 357 (296 – 657), AD APOE ε3/ε3 monocytes = 1968, median (IQR) = 217.5 (163 – 280), AD APOE ε3/ε4 monocytes = 3734, median (IQR) = 299 (114 – 470), AD APOE ε4/ε4 monocytes = 1460, median (IQR) = 214 (58 – 291). RNA-seq assay: HC APOE ε3/ε3 CD14 monocytes = 833, median (IQR) = 75 (61.5 – 127), HC APOE ε3/ε4 CD14 monocytes = 2255, median (IQR) = 127 (11 – 262), HC APOE ε4/ε4 CD14 monocytes = 1326, median (IQR) = 198.5 (85.75 – 281.25), AD APOE ε3/ε3 CD14 monocytes = 1607, median (IQR) = 62 (14 – 166), AD APOE ε3/ε4 CD14 monocytes = 1334, median (IQR) = 115 (59.5 – 168), AD APOE ε4/ε4 CD14 monocytes = 514, median (IQR) = 11 (3.5 – 40).