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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. 1 — Endogenous BACE1 generates Aβ34 in the murine brain. Endogenous levels of murine APP and/or sAPP, BACE1, and Aβ in BACE1−/−, BACE1+/−, and wild-type littermates (+/+). N = 4 animals per group. Western blot of endogenous APP and/or sAPP and BACE1 expression in male and female mice (a) and corresponding quantification of relative protein amounts of BACE1 (b) and APP and/or sAPP (c). Quantification (pg/mg total protein) of absolute amounts of Aβ34 (d), Aβ38 (e), Aβ40 (f), and Aβ42 (g) as determined by custom 4-plex MSD multiplexing assays. Ratios of Aβ34/Aβ38 (h), Aβ34/Aβ40 (i), and Aβ34/Aβ42 (j) are displayed. Statistics: b one-way ANOVA, F(2, 9) = 1021, p < 0.0001, c one-way ANOVA, F(2, 9) = 17.28, p < 0.001, d one-way ANOVA, F(2, 9) = 145.7, p < 0.0001, e one-way ANOVA, F(2, 9) = 53.68, p < 0.0001, f one-way ANOVA, F(2, 9) = 95.65, p < 0.0001, g one-way ANOVA, F(2, 9) = 49.70, p < 0.0001, h one-way ANOVA, F(2, 9) = 425.2, p < 0.0001, i one-way ANOVA, F(2, 9) = 378.0, p < 0.0001, j one-way ANOVA, F(2, 9) = 157.6, p < 0.0001. 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, ns = nonsignificant p > 0.05. For each target, the MSD software computes the lower limit of detection (LLOD) as 2.5 standard deviations above the blank