Fig 1.
Behavioral and ptau evaluation after intraperitoneal injection of blood from aged P301S and WT mice into P301S animals.
(A) The evaluation of motor activity was measured by the rotarod performance test, represented by latency to fall (s). Two tailed t-test. (B) The evaluation of working memory was measured by the Y-Maze test, represented by correct alternations (%). Two-tailed t-test. (C) Representative images of AT8 immunoreactivity in the hippocampus. Scale bars: 200 μm (c1,3), 100 μm (c2,4). (D) Quantitative analysis of burden (%) in the hippocampus and cortex. Multiple t-test were corrected using Bonferroni-Dunn method. (E) Representative images of PHF1 labeling in hippocampal sections. Scale bars: 200 μm (e1,3), 50 μm (e2,4). (F) Quantitative analysis of PHF1 burden (%) in hippocampus and cortex. Multiple t-test were corrected using Bonferroni-Dunn method. The values shown in the graphs are expressed as the mean ± SEM of the different animals used in each group (n = 4/group). *p < 0.05; **p < 0.01. Individual data points represent measurements from each animal.
Fig 2.
Glial response analysis after intraperitoneal infusion of blood from aged P301S and WT mice into P301S animals.
(A) Representative images of GFAP labeling in hippocampal sections. Scale bars: 200 μm (a1,3), 50 μm (a2,4). (B) Quantitative analysis of GFAP burden (%) in hippocampus and cortex. Multiple t-test were corrected using Bonferroni-Dunn method. (C) Representative images of Iba1 immunoreactivity in the hippocampal area. Scale bars: 200 μm (c1,3), 50 μm (c2,4). (D) Quantitative analysis of Iba1 immuno-positive burden in the hippocampus and cortex. Multiple t-test were corrected using Bonferroni-Dunn method. The values shown in the graphs are expressed as the mean ± SEM of the different animals used in each group (n = 4/group). **p < 0.01. Individual data points represent measurements from each animal.
Fig 3.
Behavioral analysis after intravenous blood infusion from old P301S and WT mice.
(A) The evaluation of motor capacity was measured by the rotarod performance test, represented by latency to fall (s). Welch’s ANOVA followed by the Games-Howell multiple comparison post-hoc test. (B) The evaluation of working memory was measured by the Y-Maze test, represented by correct alternations (%). Welch’s ANOVA followed by the Games-Howell multiple comparison post-hoc test. (C) Spatial memory was evaluated with the MWM. Acquisition performance. Animals were given four trials per day and data represent the mean ± SEM of blocks of four trials. Two-tailed t-test. (D) Quantitative analysis of short-term memory on day 5 and (E) long-term memory on day 12. Kruskal-Wallis followed by the Dunn-Bonferroni multiple comparison post-hoc test. The values shown in the graphs are expressed as the mean ± SEM (n = 8-12 animals/group). *p < 0.05.
Fig 4.
Tau histopathological analysis in P301S mice after intravenous blood infusion from P301S and WT mice.
(A) Representative images of AT8 immuno-reactivity in the hippocampus. Scale bars: 200 μm (a1,3), 100 μm (a2,4). (B) Quantitative analysis of AT8 burden (%) in the hippocampal area. Mann-Whitney U test. (C) Representative images of PHF1 immuno-reactivity in the hippocampus. Scale bars: 200 μm (c1,3), 100 μm (c2,4). (D) Quantitative analysis of PHF1 burden (%) in the hippocampal area. Two-tailed t-test. The values shown in the graphs are expressed as mean ± SEM (n = 8-12 mice/group). *p < 0.05.
Fig 5.
Tau isoform analysis in P301S mice after intravenous blood infusion obtained from P301S or WT mice.
Quantification by ELISA of ptau pS199 (A), pT181 (B), pT217 (C), and total tau ratio in plasma samples, analyzed with Welch’s t-test and Mann-Whitney U test, respectively. (D) Representative immunoblot of ptau and total tau (AT8 and HT7) in brain homogenate samples. (E) WB quantification of AT8/HT7 ratio (%). Two tailed t-test. ELISA quantification of ptau pS199 (F), pT181 (G) and total tau ratio in the brain, analyzed with Welch’s t-test and two tailed t-test, respectively. The values shown in the graphs are expressed as mean ± SEM (n = 8-12 mice/group). *p < 0.05; **p < 0.01; ***p < 0.001.
Fig 6.
Neuroinflammation analysis after intravenous infusion of blood from P301S mice.
(A) Representative images of GFAP immunostaining in the hippocampus. Scale bars: 200 μm (a1,3), 100 μm (a2,4). (B) Quantitative burden analysis of GFAP immunostaining. Mann-Whitney U test. (C) Representative images of BLBP immunoreactivity. Scale bars: 200 μm (c1,3), 100 μm (c2,4). (D) Quantitative burden analysis of BLBP immunostaining. Two-tailed t-test. (E) Representative images of Iba1 immunoreactivity in the hippocampal area. Scale bars: 200 μm (e1,3), 100 μm (e2,4). (F) Quantitative burden analysis of Iba1 immunostaining. Two-tailed t-test. (G) Representative images of CLEC7A immunolabeling. Scale bars: 200 μm (g1,3), 100 μm (g2,4). (H) Quantitative burden analysis of CLEC7A immunostaining. Two-tailed t-test. The values shown in the graphs are expressed as mean ± SEM (n = 8-12 mice/group). *p < 0.05; **p < 0.01, ***p < 0.001.