Fig. 3: Neuronal subpopulations and cortical layers selectively affected in AD.

Average cell numbers per cluster per sample, comparing either controls and AD samples from donors heterozygotic for the common TREM2 allele (a; CtrlCV, sections from n = 6 brains; AlzCV, n = 18) or controls and AD samples homozygotic for the TREM2 common allele and those heterozygotic for R62H or R47H risk variants combined (c; CtrlCV, n = 6; CtrlTREM2, n = 6; AlzCV, n = 18; AlzTREM2, n = 13) or separately (e; CtrlCV, n = 6; CtrlTREM2, n = 6; AlzCV, n = 18; AlzR62H, n = 7; AlzR47H, n = 6). Only clusters with significant differences in sizes between sample groups are shown. The density of cells (cell number/mm2) 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 carrying the common TREM2 allele (c; CtrlCV, n = 6; AlzCV, n = 18) or controls and AD samples homozygotic for TREM2 common allele and those heterozygotic for R62H or R47H risk variants combined (d; CtrlCV, n = 6; CtrlTREM2, n = 6; AlzCV, n = 18; AlzTREM2, n = 13) or considered separately (d; 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 Dirichlet regression (a,c,e), two-sided Wilcoxon signed-rank test (b), or 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 (d, f). 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.