Fig. 2

Blockade of PD-L1 overcomes loss of cognitive performance and reduces cerebral pathology in 5XFAD mice. 5XFAD mice were treated with either anti-PD-1, anti-PD-L1 or IgG. Experimental design is presented in a. b RAWM performance of WT littermates (n = 10), and of mice treated with 0.1 mg/mouse (n = 8), 0.5 mg/mouse (n = 9), or 1.5 mg/mouse (n = 9), of anti-PD-L1 antibody, or with 1.5 mg/mouse IgG (n = 10). c RAWM performance of WT (n = 19), and of 5XFAD mice treated with either 0.5 mg of anti-PD-1 antibody (n = 14), or with 0.5 mg of anti-PD-L1 antibody (n = 7); IgG control antibody (n = 6 IgG2a; n = 9 IgG2b). Two-way repeated-measures ANOVA and Dunnett’s post-hoc test for multiple comparisons between each anti-PD-1-treated group and the IgG-treated groups (*P < 0.05, **P < 0.01, ***P < 0.001) and between Anti-PD-L1 and IgG-treated groups (^#P < 0.05, ^##P < 0.01, ^###P < 0.001) . Results shown are pooled from two experiments. d–g Analysis of disease pathology from a single experiment; one hemisphere of each brain was taken for histology and one for quantitative measurements of mRNA. d Representative immunofluorescence images of brains stained for Aβ (in red), GFAP (in green) and DAPI nuclear staining (scale bars, 100 μm). e, f Quantitative analysis of Aβ in anti-PD-1-treated mice (n = 9), anti-PD-L1-treated mice (n = 7), and IgG-treated (n = 9) mice. g GFAP in anti-PD-1-treated (n = 9), anti-PD-L1-treated mice (n = 7), IgG-treated (n = 8) mice, and WT (n = 6). Plaque area and numbers were quantified in the dentate gyrus (DG) and in the cerebral cortex (layer V), and GFAP immunoreactivity was measured in the hippocampus (one-way ANOVA and Fisher’s exact test). h, i Representative immunofluorescence images, and quantitative analysis of synaptophysin in the hippocampal CA3 and in the DG, in the brains of anti-PD-1-treated mice (n = 6), anti-PD-L1-treated 5XFAD mice (n = 7), and IgG-treated mice (n = 9) (one-way ANOVA and Fisher’s exact test). Scale bars, 50 μm (h). j, k RT-qPCR, in hippocampal tissue isolated from mice treated with IgG control (n = 5), anti-PD-1 antibody (n = 5), or anti-PD-L1 antibody (n = 5) (one-way ANOVA and Fisher’s exact test). l Experimental design of the mice studied in m and n. m RAWM performance before (n = 13) treatment, and of the same mice (n) following their treatment either with 1.5 mg/mouse (n = 7) anti-PD-L1, or with IgG control (n = 6). WT littermates were tested twice (n = 7) (two-way repeated-measures ANOVA and Dunnett’s post-hoc test for multiple comparisons between anti-PD-L1 IgG-treated groups). b, c, e–g, i–k mean ± s.e.m.; *P < 0.05, **P < 0.01, ***P < 0.001. DAPI: 4′,6-diamidino-2-phenylindole, RT-qPCR: real-time quantitative PCR