Fig. 3

Transcriptional differences between AD and resilient donors become apparent at the gene-set level. A Venn diagram of DEGs: 897 between AD and control, 1121 between resilient and control and 6 between AD and resilient. Red are upregulated genes, blue downregulated genes. B Quadrant plot of fold changes between resilient versus control and AD versus control. Unique DEGs between resilient and control are highlighted in blue, between AD and control in red and between both resilient and AD versus control in green. C–E Top GSEA results between the different groups. Enriched gene sets in AD include processes related to the extracellular matrix, apoptosis and immune function, while in controls processes related to mitochondrial processes and translation are enriched. Enriched gene sets in the resilient group are related to the extracellular matrix and ciliopathies. Compared to AD, E Top GSEA enriched processes in the resilient group include changes in mitochondria and in metabolism of heavy metals. F Quadrant plot of GSEA of resilient versus AD corrected for pTau or Aβ. When corrected for either pTau or Aβ, processes related to metallothionein are enriched in the resilient group. Correcting for pTau partly removes significance of mitochondrial processes and immune functions. G Correlation matrix of top DEGs or enriched genes between resilient and AD and AD pathology. Mitochondrial genes negatively correlate with pTau pathology, while metallothionein genes and SNORD114-6 do not correlate with AD pathology. Red is negatively and blue positively correlated. Colored boxes indicate significance. H Estimated cell type proportion shows a lower proportion of inhibitory cells in the resilient and AD groups compared to the control group. Statistical significance was tested with a two-sided Student’s t test. p < 0.05: *