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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 2. Epigenetic dysregulation in AD peripheral immunity and concordance with differential gene expression.

Figure 2.

(A) DARs of chromatin between AD and HCs by cell type using single cell LR and pseudobulk DESeq2 methods. The overlapping genes from these two statistical measures are used in all downstream analyses. UpSet plot shows unique and shared DARs by cell type with a corresponding heat map showing the ratios of DARs to regions tested. (B) Proportion of AD versus HC DARs by peak type and direction of accessibility. (C) Pathway analysis of AD vs HC DARs of CD8 T cells [HC cells = 57326, median interquartile range (IQR) = 1969 (963.25 – 2771.25), AD cells = 53974, median (IQR) = 1304 (668.75 – 2682)]. indicating increased activation and cytokine signaling and reduced cellular senescence in AD. (D) DEGs between AD and HCs by cell type using MAST and pseudobulk edgeR methods. The overlapping genes from these two statistical measures are used in all downstream analyses. UpSet plot shows unique and shared DEGs by cell type with a corresponding heat map showing the ratios of DEGs to genes tested. (E) Overlapping significant genes by scATACseq and scRNAseq by cell type indicating CD14 and CD16 monocytes and CD8 TEM cells as having the most overlapping genes with altered chromatin accessibility and altered gene expression in AD.