Fig. 2

ApoeCh variant ameliorates Aβ plaque burden and plaque-induced damage in 5xFAD mice. a Representative hemispheric coronal brain images of 4-mo-old (top) and 12-mo-old (bottom) 5xFAD and 5xFAD;ApoeCh stained for dense-core plaques using AmyloGlo (green) Scale bar = 500 µm. Insets of 20 × magnification images of the subiculum. Scale bar = 100 µm. b-e Quantification of AmyloGlo⁺ plaques (4 month—b; 12 month—d) and percent AmyloGlo⁺ area coverage (4 month—c; 12 month—e) of 5xFAD and 5xFAD;ApoeCh mice. Blue bar denotes statistical significance only in males. f-m Quantification of soluble (f-i) and insoluble (j-m) Aβ in micro-dissected cortices (f, h, j, l) and hippocampi (g, i, k, m) of 12 month-old 5xFAD and 5xFAD;ApoeCh mice. n Representative confocal images of subiculum in 4-mo-old (top) and 12-mon-old (bottom) wild-type, ApoeCh, 5xFAD, and 5xFAD;ApoeCh mice immunolabeled for LAMP1 (red) for dystrophic neurites quantified in o and p. Insets show higher magnification images with LAMP1 (red) and AmyloGlo for dense-core plaques (green). Scale bar = 100 µm. Student’s t-test. q-r Measurement of plasma NfL in WT, ApoeCh, 5xFAD, and 5xFAD;ApoeCh mice at 4- (q) and 12-mo (r). n = 4–6 mice/sex/genotype. In panels with graphs, sex of individual animals is denoted by pink (female) or blue (male) circles. Data are represented as mean ± SEM. Two-way ANOVA followed by Tukey’s post hoc tests to examine biologically relevant interactions. Statistical significance is denoted by *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001