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. 2019 Jan 28;10:465. doi: 10.1038/s41467-019-08352-5

Fig. 1.

Fig. 1

Early treatment with anti-PD-1 antibody delays cognitive loss and rescues neurons in 5XFAD mice. 5XFAD mice were treated with either PD-1–specific antibody or IgG control starting at an average age of 3.5 months, and continued once a month (total of three injections). Experimental design is presented in (a). Black arrows indicate time points of treatment. Time points of cognitive testing are also indicated. b RAWM performance of 5.5-month-old anti-PD-1-treated mice (n = 7), control antibody (IgG)-treated 5XFAD mice (n = 9), and wild-type (WT) animals (n = 8). c RAWM performance of the same mice one month later (6.5-month-old). (Two-way repeated-measures ANOVA and Dunnett’s post-hoc test for multiple comparisons between the two treated groups.) d Comparison of the performance of anti-PD-1 and IgG-treated groups at 5.5 and 6.5 months; values indicating the number of errors for each mouse, taken from the last measurement on the second day of the test. e, f Representative Cresyl violet-stained images of the cortex and subiculum, and g, h quantitative analysis of IgG-treated 5XFAD mice (n = 9) as compared to anti-PD-1-treated 5XFAD mice (n = 7); the WT (n = 7) controls that were analyzed were used to calculate the percentage of surviving neurons. i, j Images and quantitative analysis of Neu-N+ neurons in the subiculum of anti-PD-1-treated 5XFAD mice (n = 7), and IgG-treated 5XFAD mice (n = 9), respectively; the WT controls (n = 7) that were analyzed were used to calculate the percentage of surviving neurons. Neuronal survival is presented relative to the number of the pyramidal neurons in the age-matched WT littermates. k, l Representative immunofluorescence images and quantitative analysis of Neu-N+ neurons (green) in the subiculum, showing increased immunoreactivity of Activated Caspase-3 (red) in IgG-treated 5XFAD mice (n = 9), in comparison to anti-PD-1-treated 5XFAD mice (n = 7) (Student’s t test). Scale bars, 50 μm (e, f), 100 μm (i), and 25 μm (k). Data are presented as mean ± s.e.m.; *P < 0.05, **P < 0.01, ***P < 0.001