Fig. 4: Sex-related transcriptomic differences in subtypes of AD.

a, Effect sizes from DSAD female versus male differential gene expression, genes stratified by chromosome and spatial region. Significant (FDR < 0.05) genes with absolute average log₂(FC) ≥ 0.25 in at least one region are shown. b, Stacked bar chart showing the number of DSAD female versus male DEGs by spatial region stratified by chromosome. c, Volcano plots showing the effect size and significance level from the DSAD female versus male DE (MAST⁵⁹, two-sided test). d, Number of DEGs upregulated in females or upregulated in males for each cluster on top and bottom, respectively. Proportional bar charts show the proportion of DEGs that are snRNA-seq marker genes. e,f, Selected pathway enrichment analysis from DEGs that were upregulated in females (e) or males (f). One-sided Fisher’s exact test was used for enrichment analysis. g, Overlap between sets of DEGs in spatial clusters. h, Representative images from the prefrontal cortex (PFC) of age-matched male and female patients with DSAD stained for C1QB (red). Dashed line visually separates GM and WM. i, Bar graph representing mean fluorescence intensity (relative) in ×20 images of C1QB (n = 5 brain sections from n = 3 female DSAD cases and n = 5 brain sections from n = 3 male cases) in the WM. P value from the two-sided t test is shown. Error bar shows one s.d. from the mean. j, Top, spatial feature plots showing C1QB expression in representative female (left) and male (right) DSAD samples. Bottom, samples colored by region annotations. k, Heatmap showing the meta-module DSAD female versus male DME results for each cortical layer and WM. X indicates a lack of significance. l, Volcano plot showing the effect size and significance level from DSAD female versus male DME analysis (two-sided Wilcoxon rank-sum test). m, Comparison of DME effect sizes between sex and diagnosis tests. Black line represents a linear regression with a 95% confidence interval around the mean shown in gray. Pearson correlation coefficients are shown in the upper left corner of each panel. Number of modules significant in either analysis in each quadrant is noted. F, female; M, male.