Fig. 3. NLRP3 or caspase-1 deficiency increases microglial Aβ phagocytosis.

(a) Quantification of Aβ phagocytosis by flow cytometry of microglia isolated from adult mice 3h after intraperitoneal injection of methoxy-X04 (n=5, mean±SEM, ANOVA, Tukey´s test, ** p<0.01) (b) Same as A with APP/PS1 and APP/PS1/Casp-1^−/− mice (n=5, mean±SEM, ANOVA, Tukey´s test, * p<0.05) (c) Immunohistochemistry staining of ASC specks in CD11b-positive microglia. H3342 is a nuclear stain. (d) Immunocytochemistry of mAb IC16 (anti-Aβ), methoxy-X04 labelled Aβ within Lamp2+ intracellular structures in CD11b+ microglia from 16 month old APP/PS1 mice. (e) Quantification of CD11b+, Aβ+ microglia in the hippocampus (HC) and frontal cortex (FC) of 16 month old mice (n=5, mean±SEM, Student's t-test, ** p<0.01) (f) Representative micrographs from methoxy-X04-treated APP/PS1 and APP/PS1/NLRP3^−/− mice stained for Iba-1 and Aβ. (g) Average IC16-positive Aβ plaque size, determined by co labelling with methoxy-XO4, was markedly reduced in APP/PS1/NLRP3^−/− mice (n=150 plaques were assessed from each group of four mice, mean±SEM, Student's t-test, *** p<0.001). A scatter blot of all plaques that was analyzed by linear regression is shown at the right (150 plaques/group; lines: linear regression analysis, dashed lines: 95% confidence intervals, R²=0.5588 for APP/PS1 and R²= 0.4431 for APP/PS1/NLRP3^−/− mice).