Fig. 3: ADAD participants exhibit distinct signatures in astrocytes, microglia, OPCs, oligodendrocytes, and neurons.
From: Single-nucleus RNA-sequencing of autosomal dominant Alzheimer disease and risk variant carriers
a–f Proportion plots show the enrichment of certain cell states in ADAD participants compared to all other participants. The proportion was calculated for each sample (see Methods). For visualization, sample proportions are averaged by AD status. (*) represents a significant (p < 0.05) enrichment of that cluster within ADAD samples as determined by linear regression. Exact p values can be found in Supplementary Dataset 6. ADAD autosomal dominant AD, sAD sporadic AD, Pres presymptomatic, CO neuropath free, OTH non-AD neurodegenerative. a Astrocytes (Astro-DAA = cluster 4). b Microglia (Mic-stress = cluster 4). c Excitatory neurons. d Inhibitory neurons. e Oligodendrocytes (Oligo-spliceosome cluster 3). f OPCs. g A heatmap of the enriched pathways within the upregulated genes for each cell state. The DEGs were isolated from the linear mixed models comparing each cell state to all other cell states of the same cell type. GO Biological Process terms were summarized and selected as described in the Methods. (·) indicates a significant (Benjamini–Hochberg p < 0.05) association as calculated by the R package enrichR. Exact p values can be found in the Source Data file. h 5xFAD mouse validation of Mic-stress ADAD cluster (cluster 2 here). Left and middle: a UMAP of integrated microglia split by species. Right: a violin plot showing that mouse cells in the ADAD cluster have a higher human microglia ADAD cluster signature score than mouse cells in other clusters. (**) = p < 5.0 × 10−25, (***) = p < 5.0 × 10−50. Source data are provided as a Source Data file.
