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Fig. 3 | Molecular Neurodegeneration

Fig. 3

From: Modeling the β-secretase cleavage site and humanizing amyloid-beta precursor protein in rat and mouse to study Alzheimer’s disease

Fig. 3

Humanization of the Aβ sequence in rat affects APP processing, while the M139T mutation in PSEN1 results in increased Aβ42 production. a Western blot analysis of APP protein in cerebrum of 14 weeks old WT, Apphu/hu and Apphu/hu;Psen1M139T+/+ rats (n = 6). B63 antibody binds to full length APP (FL APP) and C-terminal fragments (CTF, longer exposure). 82E1 antibody specifically detects human Aβ (1-16), and hence the human B-CTF, independently confirming that the rat App gene was successfully humanized. β- ACTIN was used as a loading control. b Quantification of APP protein using relative intensity (n = 6, mean ± SD, ** p = 0.009, * p = 0.017, One-Way ANOVA, Turkey post-hoc test). c ELISA analysis of soluble Aβ expressed as pg/g tissue. BD, below detection limit; ND, not determined (n = 6, mean ± SD, *** p < 0.0001, * p = 0.012, One-Way Anova, Turkey post-hoc test). d Aβ ratios for Apphu/hu and Apphu/hu;Psen1M139T+/+ indicate an impairment in γ-secretase cleavage (n = 6, mean ± SD, ***p < 0.0001 two tailed t-test). e Immunoblot of total MAPT in rat cerebrum with the 3Rtau-specific antibody RD3, the 4Rtau-specific antibody RD4 and an antibody detecting total tau. The MAPT ladder shows recombinant human MAPT (0N3R, 0N4R, 1N3R, 1N4R, 2N3R, 2N4R). Notice that rat MAPT proteins migrate faster than the corresponding human splice variants. β- ACTIN was used as the loading control. f Quantification of MAPT relative to WT samples ((n = 6, mean ± SD)

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