The density of cells (cell number/mm 2 ) in each cortical layer (L1-6) from all clusters showing layer-specific vulnerabilities (distribution of all neuronal clusters shown in Figure S5.b ), comparing either controls and AD samples homozygotic for TREM2 common allele and those heterozygotic for R62H or R47H risk variants combined (CtrlCV, n = 6; CtrlTREM2, n = 6; AlzCV, n = 18; AlzTREM2, n = 13) or considered separately (CtrlCV, n = 6; CtrlTREM2, n = 6; AlzCV, n = 18; AlzR62H, n = 7; AlzR47H, n = 6). Quantification was performed on three ROIs acquired from a single section of each sample and pooled together before performing statistical analyses between groups. Statistical significance was calculated with either ANOVA and two-sided Tukey tests or Kruskal–Wallis and two-sided Wilcoxon signed-rank test, depending on whether groups showed normal or non-normal distributions, respectively. Boxplots show median (middle line), interquartile range (box), and variability outside of the first and third quartile (lines extending from the box). P values are indicated as: non-significant, ns, p > 0.05; * p ≤ 0.05; ** p ≤ 0.01; *** p ≤ 0.001; **** p ≤ 0.0001. Source data are provided as a Source Data file.