Fig. 2: Regional heterogeneity of astrocyte transcriptome in the normal aging brain.

a, Venn diagrams show the DEGs—upregulated in red and downregulated in blue—in each brain region relative to all other brain regions in n = 8 donors at pathology stage 1 (no neuritic plaques and Braak NFT stages 0/I/II). b, Heatmap depicts the DEGs in each brain region (upregulated in red and downregulated in blue) ranked by average log FC. c, Fluorescence immunohistochemistry of AQP4 and connexin-43 (GJA1) in EC and V1. Automated immunohistochemistry with the peroxidase-DAB method followed by quantification of AQP4- and GJA1-immunoreactive percentage area fraction in EC and V1 formalin-fixed paraffin-embedded (FFPE) sections from n = 11 pathology stage 1 donors (including two donors from this snRNA-seq study) demonstrated a higher expression of these two proteins in EC versus V1, in agreement with the snRNA-seq results. *P = 0.05, **P = 0.0036, two-sided paired t test. Scale bars—EC, 1 mm; V1, 5 mm; insets, 500 μm. d, Volcano plot illustrates the correlation analysis between pTau/tau ratio and astrocyte gene expression levels in pathology stage 1 donors. The x axis represents the correlation coefficient β, while the y axis indicates the FDR (expressed as −log₁₀(FDR)). Genes in red are positively correlated, and those in blue are negatively correlated at an FDR < 0.05 (−log₁₀(FDR) > 1.3), whereas genes in gray were statistically NS. e, Venn diagrams show the number of genes upregulated in EC (EC high) and/or positively correlated with the pTau/tau ratio (top) and the number of genes downregulated in EC (EC low) and/or genes negatively correlated with pTau/tau ratio (bottom). Genes in each intersection are listed in the boxes. NS, not significant.