Fig. 6.
Aggravated MAPT pathology in 6 month-old 5xFAD;Cx3cr1−/− mice. Distribution of AT8+ pTau in 6 month-old (A) B6;Cx3cr1+/+, B6;Cx3cr1−/− and (B) 5xFAD;Cx3cr1+/+, 5xFAD;Cx3cr1−/− mice. α-AT8 was used to label (6B-i) neuronal (solid arrows) and axonal (dashed arrows) pathology in cortical layer III, (6B-ii) dystrophic neurites in cortical layer V, (6B-iii) neuronal inclusions in CA2/3 and (6B-iv) neuritic plaques in the subiculum of 6 month old (top panels) 5xFAD;Cx3cr1+/+ and (bottom panels) 5xFAD;Cx3cr1−/− mice. Images representative of pTau pathology in n = 6 mice (3 females, 3 males) in each genotype. Scale bars in A,B(i)-A(iii) = 50 µm. Scale bars in A,B(iv) = 100 µm. (C) Quantification of %AT8+ areas in the cortex, hippocampus, and subiculum of 6 month-old 5xFAD;Cx3cr1+/+ (black bars) and 5xFAD;Cx3cr1−/− mice (grey bars). Data represents histological analyses performed using multiple, serial sections from n = 6 mice (3 females, 3 males), of each genotype. Error bars in C represent SEM. Statistical analysis for done using One-way Anova followed by Brown-Forsythe and Welch’s post-hoc tests. *padj < 0.01, **padj < 0.002. (D) Pearson’s Correlation analysis between %AT8+ Tau and %OC+ oAβ in cortices of 6 month-old 5xFAD;Cx3cr1+/+ and 5xFAD;Cx3cr1−/− mice. (E) Western blot analyses to quantify the levels of soluble AT8+ pTau in the cortex of 6 month old 5xFAD;Cx3cr1+/+, 5xFAD;Cx3cr1−/− and their genotype matched B6 controls. Blots representative of n = 6 (3 females, 3 males) per genotype. (F) Densitometric analysis to quantify fold changes in Tau5+ (total tau) and AT8+ (pTau) in the cortex of 6 month-old B6;Cx3cr1+/+ (white bars), B6;Cx3cr1−/− (light grey bars), 5xFAD;Cx3cr1+/+ (black bars) and 5xFAD;Cx3cr1−/− (dark grey bars) mice. Data for AT8 represents fold change in AT8 normalized to total tau levels. Error bars represent SEM. Statistical analysis for done using One-way Anova followed by Brown-Forsythe and Welch’s post-hoc tests. *padj < 0.01, **padj < 0.002, ***padj = 0.0002, ****p.adj < 0.0001