hTFR1/5xFAD

Fig.1 Blood routine test in 6-week-old hTFR1/5×FAD mice. (n=9-10 males and females). 

At 6 weeks of age, hTFR1/5×FAD mice showed marked changes in erythrocyte indices, while hematocrit and leukocyte counts remained broadly comparable to those of sex-matched WT controls. The findings did not suggest severe anemia or marked leukocyte depletion.

Fig.2 Blood Biochemistry  in 6-week-old hTFR1/5xFAD mice (n=7-10 males and females). 

Except for the elevated serum iron associated with hTfR1 humanization, major indicators of hepatic and renal function were broadly comparable to those of sex-matched WT controls, with no clear biochemical evidence of overt systemic organ dysfunction.

Fig.3 Blood routine test in 4-month-old hTFR1/5×FAD mice. (n=4-6 males). At 4 months of age, hTFR1/5×FAD mice retained the microcytic, hypochromic erythrocyte profile observed in an independent 6-week cohort relative to their respective WT controls. Hemoglobin was lower than in age-matched WT mice, whereas leukocyte and fluorescence-based platelet counts showed no marked reduction.

Fig.4 Blood routine test in 4-month-old hTFR1/5×FAD mice. (n=4-6 males). At 4 months of age, hTFR1/5×FAD mice retained the microcytic, hypochromic erythrocyte profile observed in an independent 6-week cohort relative to their respective WT controls. Hemoglobin was lower than in age-matched WT mice, whereas leukocyte and fluorescence-based platelet counts showed no marked reduction.

Fig.5 Blood routine test in 4-month-old hTFR1/5×FAD mice. (n=4-6 males). At 4 months of age, hTFR1/5×FAD mice retained the microcytic, hypochromic erythrocyte profile observed in an independent 6-week cohort relative to their respective WT controls. Hemoglobin was lower than in age-matched WT mice, whereas leukocyte and fluorescence-based platelet counts showed no marked reduction.

Fig.6 Blood Biochemistry  in 6-week-old hTFR1/5xFAD mice (n=5-6 males). 

Except for the elevated serum iron associated with hTfR1 humanization, major biochemical indicators in 4-month-old male hTFR1/5×FAD mice were generally maintained relative to age-matched WT controls, with no clear evidence of overt systemic organ dysfunction. 

Fig.7 Age-dependent accumulation and aggregation of Aβ amyloid were observed in the brains of hTFR1/5xFAD mice.

Fig.8 The effect of RG6102 on nesting building performance in hTFR1/5xFAD mice. Compared to hTFR1/5xFAD(HO/WT) mice, hTFR1/5xFAD(HO/HE) mice displayed impaired nesting ability, with significantly lower nesting scores (*P < 0.05; **P < 0.01). 

Fig.9 The effect of RG6102 on reducing Aβ deposition in the hippocampus of hTFR1/5xFAD mice. Compared to hTFR1/5xFAD mice treated with vehicle, the group treated with RG6102 showed a significantly reduction in the 6E10-positive area in hippocampus, suggesting a decrease in Aβ deposition following the administered dosing regimen (***P < 0.001).

Fig.10 The effect of RG6102 on reducing Aβ deposition in the cortex of hTFR1/5xFAD mice. Compared to hTFR1/5xFAD mice treated with vehicle, the group treated with RG6102 showed a significantly reduction in the 6E10-positive area in cortex, suggesting a decrease in Aβ deposition following the administered dosing regimen (**P < 0.01, ****P < 0.0001).

Fig.11 The effect of RG6102 on Aβ42/40 ratio in hTFR1/5xFAD mice. Compared to hTFR1/5xFAD mice treated with vehicle, hTFR1/5xFAD mice treated with RG6102 displayed higher plasma (A) and CSF (B) Aβ42/40 ratio, as well as higher insoluble Aβ42/40 ratio in both hippocampus (C)  and cortex (D) , a decreasing trend in soluble Aβ42/40 ratio in the hippocampus (E) , and no significant change in soluble Aβ42/40 ratio in the cortex (F) (**P < 0.01, ****P < 0.0001).

Fig.12 The effect of RG6102 on reducing Aβ deposition in the hippocampus of hTFR1/5xFAD mice. Compared to the vehicle control group (G1), the group treated with RG6102 (G2) showed a consistent reduction in the 6E10-positive area in hippocampus across all measured time points, suggesting a decrease in Aβ deposition.

Fig.13 The effect of RG6102 on reducing Aβ deposition in the Cortex of hTFR1/5xFAD mice. Compared to the vehicle control group (G1), the group treated with RG6102 (G2) showed a consistent reduction in the 6E10-positive area in cortex across all measured time points, suggesting a decrease in Aβ deposition.