When plasma levels were compared across APOE genotype groups, significant differences were seen in the levels of 17 proteins (in descending order of significance): ApoE, interleukin (IL) 13, epidermal growth factor, IL-15, IL-3, tissue inhibitor of metalloproteinase 1, I-309 (CC chemokine 1), basic fibroblast growth factor, superoxide dismutase 1 (SOD1), chromogranin A, RANTES, CD5 antigen–like, IL-5, brain-derived neurotrophic factor, AXL receptor tyrosine kinase, IL-12p40, and IL-4 (Table 1). Total levels of ApoE were significantly elevated in persons with the APOE ϵ2/3 genotype relative to the ϵ3/3 genotype (67.4 vs 34.1 μg/mL; P = .002) and higher in carriers of the ϵ3/3 relative to the ϵ3/4 genotype (34.1 vs 27.3 μg/mL; P = .02) (Figure 1A). Levels of IL-13 were significantly elevated in persons with the ϵ3/3 relative to the ϵ2/3 genotype (65.6 vs 31.9 pg/mL, P = .005) and higher in persons with the ϵ3/4 relative to the ϵ3/3 genotype (85.9 vs 65.6 pg/mL; P = .005) (Figure 1B). The trend for higher plasma interleukin levels in APOE ϵ3/4 carriers relative to APOE ϵ3/3 carriers and APOE ϵ3/3 carriers relative to APOE ϵ2/3 carriers held for IL-3, IL-4, IL-5, and IL-12p40 (Figure 1C, D, E, and F, respectively). Levels of I-309 were significantly elevated in persons with the APOE ϵ3/3 relative to ϵ2/3 genotype (291.7 vs 108.1 pg/mL; P = .02) and in carriers of the APOE ϵ3/4 relative to the ϵ3/3 genotype (614.8 vs 291.7 pg/mL; P = .02) (Figure 1G). The SOD1 levels were significantly higher in APOE ϵ2/3 carriers than in ϵ3/3 carriers (121.2 vs 73.5 ng/mL; P = .02) and in ϵ3/3 carriers than in ϵ3/4 carriers (73.5 vs 60.8 ng/mL; P = .02 (Figure 1H). When covariance analysis was performed for the gene with risk for mutation, the levels of 13 proteins were still significantly related to APOE genotype, although 13 proteins also showed a relationship to the gene containing the mutation. There were significant interactions between APOE genotype and FAD mutation status in the levels of ApoE, IGF-1, IL-13, IL-1α, thrombopoietin, AXL receptor tyrosine kinase, Fas ligand, IL-12p40, IL-3, IL-4, IL-5, IL-7, and MDC (Table 1).