Figure 3. Impairment of microglial phagocytosis in APPPS1 mice correlates with Aβ plaque deposition.

(A) Aβ plaque load (brain area covered by Thiazine red-positive plaques) and relative microglial phagocytic activity normalized to corresponding wildtype littermate in the cortex of 7–9 week, 4 and 9 month old APPPS1 mice. 7–9 week old mice were sub-classified according to apparent 4G8 positive plaque deposition as with (+) or without (−) detectable plaque load. (B) Correlation between extent of plaque load and relative microglial phagocytic activity in the cortex of APPPS1 mice. (C, D) Thiazine red-covered area and relative phagocytic activity of microglia in the hippocampus of 7–9 week and 4 month old mice (C) and in the cerebellum of 4 month old APPPS1 mice (D). Absolute values of microglial phagocytic indices from APPPS1 mice were normalized to wildtype littermate controls (3–4 mice per age group and genotype, ***p<0.001). (E) Phagocytic index (3 independent experiments, p = 0.181) and representative images of primary microglial cultures from wildtype and APPPS1 mice. Microglia (Iba-1, red), nuclei (DRAQ5, blue) and microspheres (green). All data are mean ± s.e.m, *p<0.05, **p<0.01. a.u. = arbitrary units. Scale bars: 10 µm.