Research Paper Volume 13, Issue 5 pp 6634—6661

CRISPR/Cas9-mediated CysLT1R deletion reverses synaptic failure, amyloidosis and cognitive impairment in APP/PS1 mice

CysLT1R deficiency inhibits amyloidogenesis in APP/PS1 mice hippocampus. (A)The triton-soluble fractions and (B) the guanidine-soluble fractions of Aβ1-40 and Aβ1-42 in mice hippocampus were assessed by ELISA. (C) Aβ immunostaining with 4G8 antibody in hippocampus of mice. Scale bar = 200 μm. (D) The percentage of area covered by Aβ deposition was quantified. (E) Representative immunoblots of APP, CTFα, CTFβ, PS1 and BACE in the hippocampus of mice. Quantifications of (F) APP, (G) CTFα, (H) CTFβ, (I) PS1 and (J) BACE were expressed as the ratio (in %) of WT group. (K) Representative immunoblots of IDE and NEP in the hippocampus of mice. Quantifications of (L) IDE and (M) NEP were expressed as the ratio (in %) of WT group. All values are expressed as mean ± SEM, n = 4-6, #P##P###P

Figure 3. CysLT1R deficiency inhibits amyloidogenesis in APP/PS1 mice hippocampus. (A)The triton-soluble fractions and (B) the guanidine-soluble fractions of Aβ1-40 and Aβ1-42 in mice hippocampus were assessed by ELISA. (C) Aβ immunostaining with 4G8 antibody in hippocampus of mice. Scale bar = 200 μm. (D) The percentage of area covered by Aβ deposition was quantified. (E) Representative immunoblots of APP, CTFα, CTFβ, PS1 and BACE in the hippocampus of mice. Quantifications of (F) APP, (G) CTFα, (H) CTFβ, (I) PS1 and (J) BACE were expressed as the ratio (in %) of WT group. (K) Representative immunoblots of IDE and NEP in the hippocampus of mice. Quantifications of (L) IDE and (M) NEP were expressed as the ratio (in %) of WT group. All values are expressed as mean ± SEM, n = 4-6, #P<0.05, ##P<0.01, ###P<0.001 vs. APP/PS1 mice.