Fig. 1
Alterations of APP cleavage and Aβ levels in AppSAA knock-in mice. a RT-qPCR analysis of brain RNA shows normal App mRNA level in the AppSAA homozygous mice (KI/KI), heterozygous mice (KI/+) and wild-type mice (+/+) at 2-month-old. b Western blotting analysis of brain lysates at 2-month-old shows normal expression of full-length APP proteins in all three genotypes and KI gene dosage-dependent increase of human full-length APP proteins and APP-CTF in KI/KI and KI/+ mice. β-Actin was used as internal loading control. c Measurement of Aβ40 and Aβ42 in brain insoluble and soluble fractions extracted from animals at 4 months of age. Level of insoluble Aβ42 is increased in KI/KI homogenates and level of insoluble Aβ40 is reduced in KI/KI and KI/+ homogenates relative to wild-type control. The insoluble Aβ42/Aβ40 ratio is significantly enhanced in KI/KI brains. Level of soluble Aβ42 is unchanged in KI/KI homogenates and level of soluble Aβ40 is reduced in KI/KI and KI/+ homogenates relative to wild-type control. The soluble Aβ42/Aβ40 ratio is significantly increased in KI/KI brains. d Measurement of Aβ40 and Aβ42 in CSF and plasma collected from mice at 4 months of age. Level of Aβ42 is unchanged in KI/KI CSF while level of Aβ40 is reduced in KI/KI and KI/+ CSF relative to wild-type control. The CSF Aβ42/Aβ40 ratio is significantly increased in KI/KI CSF. Level of Aβ42 is unchanged in KI/KI plasma while level of Aβ40 is reduced in KI/KI and KI/+ plasma relative to wild-type control. The plasma Aβ42/Aβ40 ratio is significantly increased in KI/KI. Graphs are box and whisker plots and P values: one-way ANOVA with Dunnett’s multiple comparison test, each group compared to the AppSAA +/+ control group; **P < 0.01, and ***P < 0.001. Sample size: 3-6 per genotype.