LC-MS analysis of immunoprecipated cortical amyloid-β from formic acid fraction normalised to weight of cortical tissue, was used to determine if the Dp3Tyb region was sufficent to alter the abundance of putative BACE2 cleavage products at 3-months of age. (A)
Dp3Tyb;AppNL-F/NL-F cortex weighs more than AppNL-F/NL-F cortex at 3-months of age (F(1,22) = 7.772, p = 0.011). AppNL-F/NL-F (female n = 8, male n = 5), Dp3Tyb;AppNL-F/NL-F (female n = 4, male n = 9). No significant increase in the abundance of (B) amyloid-β1-19, (F(1,20) = 0.166 p = 0.688), (C) amyloid-β1-20 (F(1,20) = 0.274 p = 0.607) or (D) amyloid-β1-34 (F(1,20) = 0.005 p = 0.942) was observed. No difference in the abundance of (E) amyloid-β1-4, (F(1,15) = 1.622, p = 0.222), (F) amyloid-β1-15, (F(1,19) = 0.496, p = 0.490), (G) amyloid-β1.16, (F(1,19) = 2.274, p = 0.148) or (H) amyloid-β1.17, (F(1,19) = 0.079, p = 0.781) was detected in the cortex of Dp3Tyb;AppNL-F/NL-F compared with AppNL-F/NL-F mice. AppNL-F/NL-F (female n = 8, male n = 5), Dp3Tyb;AppNL-F/NL-F (female n = 4, male = 9). Dp3Tyb abbreviated to Dp3 for clarity. Error bars show SEM, data points are independent mice. For amyloid-β1-19 and Amyloid-β1-20 n = 1 sample was below the limit of detection per genotype. Amyloid-β1-4 n = 3 samples were below the limit of detection per genotype, amyloid-β1-15, 1-16, 1-17 n = 1 samples were below the limit of detection per genotype. These samples are shown on the graphs but were excluded from ANOVA.