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. 2019 May 20;10:2240. doi: 10.1038/s41467-019-10152-w

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — Pharmacological inhibition of Aβ34 generation in rats. Endogenous levels of APP and/or sAPP, BACE1, and Aβ in rats 1 h after intravenous injection of the indicated concentrations (mg/kg) of the BACE1-specific inhibitor (MK-8931) n = 9 animals per group or vehicle n = 8 animals. Western blot of endogenous APP and/or sAPP and BACE1 expression (a) and corresponding quantification of relative protein amounts of APP and/or sAPP (b). Quantification (pg/mg total protein) of absolute amounts of Aβ34 (c), Aβ40 (d), and Aβ42 (e) as determined by custom MSD multiplexing assays. Ratios of Aβ34/Aβ40 (f) and Aβ34/Aβ2 (g) are displayed. Quantification of CSF levels of Aβ34 (h), Aβ38 (i), Aβ40 (j), and Aβ42 (k), as well as display of the ratios Aβ34/Aβ38 (l), Aβ34/Aβ40 (m), and Aβ34/Aβ42 (n). Statistics: b one-way ANOVA, F(4, 39) = 0.63, p > 0.05, c one-way ANOVA, F(4, 39) = 22.40, p < 0.0001, d one-way ANOVA, F(4, 39) = 12.81, p < 0.0001, e one-way ANOVA, F(4, 39) = 9.38, p < 0.0001, f one-way ANOVA, F(4, 39) = 25.93, p < 0.0001, g one-way ANOVA, F(4, 39) = 8.02, p < 0.0001, h one-way ANOVA, F(4, 39) = 26.55, p < 0.0001, i one-way ANOVA, F(4, 39) = 2.69, p < 0.05, j one-way ANOVA, F(4, 39) = 1.71, p > 0.05, k one-way ANOVA, F(4, 39) = 1.09, p > 0.05, l one-way ANOVA, F(4, 39) = 6.87, p < 0.001, m one-way ANOVA, F(4, 39) = 7.36, p < 0.001, n one-way ANOVA, F(4, 39) = 6.74, p < 0.001. Bars and error bars indicate mean ± s.e.m. Tukey’s post-hoc tests were performed for pairwise comparisons; selected comparisons are highlighted ***p < 0.001, **p < 0.01, *p < 0.05, ns = nonsignificant p > 0.05