Fig. 1

A Sex, age at onset (AAO), and age at death (AAD) of early-onset sporadic AD (onset age < 60 years), late-onset sporadic AD (onset age > 70 years), and nondemented control (NDC) patient Occipital Lobe samples. B Cluster dendrogram of all AD samples based on the expression of genes (8934) with 10 cpm across all samples. C DEqual plot of correlation between differential expression (relative to NDC) and reference patient brain RNA degradation in the 4 clusters. D Multi-Dimensional Scaling (MDS) plot of all patient samples for the top two dimensions. E Transcriptome assignment % (kallisto) across the sample groups. F AAO (left) and AAD (right) across the sample groups. G RNA-seq Volcano plots for the three AD clusters. Left, downregulated DEGs; right, upregulated DEGs. H Ranked enrichment analysis of gene expression signatures for the three AD clusters using the GOBP, Hallmark, Reactome, and StringDB databases by the tmod CERNO (left) and fgsea enrichment test (right); plotted data indicates adj. P < 0.05. I TFs with predicted significant activity change by ISMARA motif analysis curated into canonical ontological categories; [z-score] > 2 in at least one cluster shown. J GSVA heatmap, dendrogram, and gene size of the 22 co-expression modules identified by CEMiTool across the sample groups. K Camera enrichment analysis of the 22 co-expression modules in the three clusters relative to NDC; * = adj. P < 0.05. L StringDB PPI interaction networks for ontologically- and expression-related comodules across the three clusters; genes color-coded by limma t-value; upper right subpanel indicates number of DEGs within the comodule for each AD cluster. M Top enriched pathways and TFs for each comodule (hypergeometric test)