Fig. 3

Characterization of microglia response. The APOE ε4 allele is associated with enhanced microglia activation resulting from 10D5 mAb immunization compared to other APOE genotypes. a Representative microphotographs of Iba1 positive microglia in the brain cortex from untreated Age control APP/ε2 and APP/ε4 mice, and APP/ε2 and APP/ε4 mice receiving TY11-15 an IgG2a isotype control antibody or 10D5 anti-Aβ mAb. Anti-Iba1 immunostaining is visualized by red color while green color reflects counterstaining of fibrillar Aβ parenchymal plaques with Th-S. b Unbiased quantification of Iba1 positive cell load in the neocortex and (c) Iba1 load normalized to Th-S positive fibrillar plaque load across APOE genotypes and treatment arms. d Representative microphotographs of CD68 positive microglia associated with Aβ parenchymal plaques from Age control, TY11-15 or 10D5 treated APP/ε2 and APP/ε4 mice. Anti-CD68 immunostaining and Th-S staining of fibrillar Aβ plaques are visualized by red and green colors, respectively. e Unbiased quantification of CD68 positive cell load in the neocortex and (f) CD68 positive cell load normalized to Th-S positive parenchymal plaque load across APOE genotypes and treatment arms. Values shown in (b), (c), (e), and (f) represent mean ± SEM from n = 11-14 measurements/group. (b), (c), (e), and (f) p < 0.0001 (one-way analysis of variance); *p < 0.05, **p < 0.01, and ****p < 0.0001, TY11-15 control vs. 10D5 mAb treatment for matching APOE genotype (Sidak’s post hoc test). Differences between Age control and TY11-15 groups were non-significant for all matching APOE backgrounds (Sidak’s post hoc test); not shown on the graph. ^#### p < 0.0001, TY11-15 APP/ε4 control vs. TY11-15 APP/ε2 or APP/ε3 controls (Sidak’s post hoc test). ⁺⁺ p < 0.01 and ⁺⁺⁺⁺ p < 0.0001, 10D5 mAb treated APP/ε4 mice vs. 10D5 mAb treated APP/ε2 or APP/ε3 mice (Sidak’s post hoc test). ^♦ p < 0.05, 10D5 mAb treated APP/ε2 mice vs. 10D5 mAb treated APP/ε3 mice (Sidak’s post hoc test). Scale bars 50 μm (a) and 25 μm (d)