Figure 6.
LOY frequency is elevated in AD microglia across the entorhinal cortex (EC) and somatosensory cortex (SSC). (A) UMAP projection and cell type annotations using snRNA-seq from 48,748 AD and nondisease control brain tissue nuclei (GEO: GSE160936) (Smith et al. 2022). (B) LOY frequency in each brain sample for microglia, astrocytes, and neurons. Donors are ordered by AD diagnosis, AD (left) and nondisease control (right). Each donor was sampled from both the EC and SSC. (Bottom) Heatmap displaying additional phenotypic information of each donor/sample. Provided measures of amyloid percentage, Braak score, and pTau percentage were all determined using quantitative image analysis. (C) Microglia nuclei from the SSC (top) and EC (bottom) were integrated and clustered using Seurat. Subclusters were annotated using microglia gene panels (Supplemental Table S8). Homeostatic subclusters (H) are colored in various blues; inflammatory subclusters (I) are colored in oranges; and disease-associated microglia (DAM) clusters are colored in magentas. (D,F) UMAP reductions of SSC (D) and EC (F) showing LOY nuclei clustering patterns facetted by AD diagnosis. Nuclei are colored by LOY (red) and non-LOY/normal (gray). LOY nuclei frequencies are provided at the bottom of each UMAP plot. (E,G) Comparison of UMI counts (nUMI) and detected genes (nGenes) between LOY and normal nuclei. Sequencing attributes do not differ significantly between microglial LOY and normal populations. Wilcoxon test: (ns) P > 0.1, (*) P < 0.1.