Fig. 4: Distinct brain capillary endothelial states associate with healthy aging versus neurodegenerative diseases.

a, UMAP clustering representation of brain EC subtypes, encompassing capillaries, veins and arteries, derived from 70,006 EC nuclei from 92 donors, 38,218 of these contain inCITE-seq antibodies, with disease state regressed out. b, Heatmap showing identification markers for capillary EC subtypes. Green, artery; orange, vein; blue, capillary; red, capillary.2. c, In silico isolation of capillary nuclei with inCITE antibody labeling and UMAP clustering based on batch-corrected gene expression patterns and without regression of disease state. Data represent 23,152 nuclei from 47 donors. d, UMAP feature plots showing markers of the REV1 population. e,f, Scatter-plot showing correlation (Spearman, two sided) between donor age and contribution to each capillary cluster (e) and box plot showing the proportions of capillary ECs for each donor falling into each cluster (f). g, Plot showing pathway enrichment from MSigDB in disease-associated REV1 cluster versus HC cluster, by GSEA. Color bar is normalized enrichment score. Analysis of variance (ANOVA) with a post hoc Tukey test was used to compare the proportion of donor’s cell per cluster (f). P values represent comparison to healthy aged donors. REV1 (AD P = 0.011; ALS P = 0.022; FTD P = 0.012). REV2 (NS). CapA (AD P = 0.002; ALS P = 0.008; FTD NS). HC (AD P = 0.0001; ALS P = 0.0001; FTD 0.0002). CapV (NS). ***P < 0.001; **P < 0.01; *P < 0.05; NS, not significant.