Fig. 4

TWD and T2D alter microglial response to β-amyloid plaques in AD mice and human brain biopsies. a Representative immunofluorescence images of β-amyloid plaques stained with X-34 (blue) surrounded by Iba1 positive microglia (red) and lysosomes stained with Cd68 (green) from A+Tw and A+T+ mice from both STD and TWD groups. Scale bar 10 μm. b Quantification revealed that TWD significantly (p < 0.05) decreased Iba1 positive area (pixels) as compared to STD in both A+Tw and A+T+ mice, while diet showed no effect on Cd68 positive area. c Also, intensity of both Iba1 and Cd68 (arbitrary units) was significantly decreased (p < 0.001, both) in mice with TWD as compared to STD in both genotypes. Furthermore, T+ transgene (Tau P301L) significantly increased both Iba1 and Cd68 intensity (p < 0.001, both). d Representative immunofluorescence images of Iba1 positive microglia (red) and p85α staining (green) around β-amyloid plaques in hippocampus of A+T+ mice from both STD and TWD groups. Scale bar 10 μm. e Quantification of p85α revealed statistically significant genotype x diet interaction (p < 0.001) in both p85α area and p85α intensity. T+ transgene significantly increased both p85α area (p < 0.001) and p85α intensity (p = 0.007), while diet had opposing effects on p85α depending on the genotype. a-e results are shown as mean + SEM, n = 5–6 mice/group, Two-Way ANOVA. f Representative image of frontal cortex biopsy sample from probable iNPH subject co-stained for IBA1 (brown) and β-amyloid (red). White arrows denote microglia within the plaque area, and black arrow denotes microglia around the plaque area. Scale bar 10 μm. g Quantification of IBA1-positive microglia within and around the β-amyloid plaque. h Quantification of IBA1-positive microglia within the plaque area. g-h; results are shown as mean ± SEM, n = 3–5 subjects/group. AwTw = wild-type, AwT+ = Tau P301L, A+Tw = APPswe/PS1dE9, A+T+ = APPswe/PS1dE9 x Tau P301L