(A) Table showcasing the percentages of different APOE genotypes within NCI and each class. The corresponding number of cases with each genotype is also provided in parentheses. Cases considered low-risk E2 carriers or high-risk E4 carriers are indicated. Class C comprised twice as many high-risk E4 carriers compared to Classes A and B. (B) Comparison of average APOE risk scores across NCI and the three proteomic classes. Individual risk scores for each case were calculated by assigning −1 points to each E2 allele, 0 points to each E3 allele, and +1 points to each E4 allele. The ANOVA p value across groups is provided with asterisks indicating statistically significant Tukey post hoc pairwise comparisons (*, p < 0.05; **, p < 0.01; ***, p < 0.001). (C) Comparison of polygenic risk scores across NCI and the three proteomic classes. The ANOVA p value across groups is provided with asterisks indicating statistically significant Tukey post hoc pairwise comparisons (*, p < 0.05; **, p < 0.01; ***, p < 0.001). (D-E) Volcano plots displaying the log2 fold change (x-axis) against the t-test-derived -log10 statistical p value (y-axis) for proteins differentially expressed in E2 carriers or E4 carriers when compared to all other cases, excepting those with E2/4 genotypes which were excluded from these analyses. Thus, (D) is a comparison of protein expression in the 34 cases with E2/2 and E2/3 genotypes to the 313 cases with E3/3, E3/4, and E4/4 genotypes, while (E) is a comparison of protein expression in the 84 cases with E3/4 and E4/4 genotypes to the 263 cases with E2/2, E2/3, and E3/3 genotypes. Proteins are shaded according to color of module membership. (F-G) Correlation plots of module abundance levels (z-scores) in E2 (E2/2, E2/3) or E4 (E3/4, E4/4) carriers to those of each proteomic class. Class-specific z-scores in (F) reflect all members of each class, while those in (G) reflect only individuals with E3/3 genotypes in each class. Bicor correlation coefficients with associated p values are shown for each correlation plot. Abbreviations: Post-Syn Dens, Post-Synaptic Density; Metab, Metabolism.