Fig. 9.

BACE1-mediated cleavage of CHL1 is reduced in old 5XFAD mice. a Representative immunoblot of hippocampus homogenates from 12 months old GGA3WT, GGA3Het, GGA3KO, GGA3WT;5XFAD, GGA3Het;5XFAD, and GGA3KO;5XFAD male and female mice probed with anti-N-terminal CHL1 antibody (AF2147) and anti-β-tubulin (JDR.3B8). b-c The graphs represent CHL1_FL levels normalized to the levels of β-tubulin in samples from six different genotypes of male and female mice separately. Among all GGA3 genotypes, CHL1_FL levels were significantly increased in both male and female 5XFAD mice compared to gender-matched non-5XFAD mice, and such increase was more pronounced in females than males (c). d-e The graphs represent levels of CHL1_βNTF/β-tubulin levels normalized to the levels of β-tubulin in samples from six different genotypes of male and female mice separately. Both male and female 5XFAD mice have increased CHL1_ β NTF levels compared to non-5XFAD mice. However, CHL1_β NTF levels were similar in both males and females (e). f-g The graphs represent the ratio of CHL1_βNTF to CHL1_FL in the six different genotypes of male and female mice separately. The CHL1_βNTF/ CHL1_FL ratio was increased in both male and female GGA3KO mice compared to sex-matched GGA3WT littermates. In contrast, the CHL1_βNTF/CHL1_FL ratio was significantly decreased in 5XFAD mice compared to genotype-matched non-5XFAD mice and such decrease was greater in females than males (g). Total number of mice in each group is indicated within bars. All graphs represent mean ± SEM. One-way (b, d, and f) or Two-way ANOVA (c, e, and g) with Fisher’s LSD post hoc tests were applied to each sex or genotype group. * p < 0.05, ** p < 0.01, *** p < 0.001, **** < 0.0001