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. 2023 Sep 6;14:5471. doi: 10.1038/s41467-023-41283-w

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© The Author(s) 2023

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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — A, B Immunofluorescent staining of Aβ (red) and Th-S (green) in the frontal cortex region of brains, Th-S (green) and T22 (red) in the hippocampus CA1 region of brains from 6-month-old AD humanized Abx-treated mice and HC humanized Abx-treated mice. Scale bar: 40 μm. C Quantitative analysis of Aβ and Th-S positive plaques (left panel, n = 8 biologically independent samples in each group, data are shown as mean ± SEM. one-way ANOVA and Bonferroni’s multiple comparison test). A high magnification picture showed Aβ plaques (Arrow) were significantly increased in AD humanized Abx-treated mice brain (right panel, Scale bar: 10 μm). D Quantitative analysis of T22 and Th-S positive PHFs (left panel, n = 8 biologically independent samples in each group, data are shown as mean ± SEM. one-way ANOVA and Bonferroni’s multiple comparison test). A high magnification picture showed PHF Tau (Arrowhead) were significantly increased in AD humanized Abx-treated mice brain (right panel, Scale bar: 10 μm). E Aβ₄₀ and Aβ₄₂ concentrations in the cortex of AD or HC humanized Abx-treated mice were measured using mouse Aβ₄₀ and Aβ₄₂ ELISA kit. the concentration of Aβ₄₂, not Aβ₄₀ was significantly increased in AD humanized Abx-treated mice compared with HC humanized Abx-treated mice cortex. (n = 5 biologically independent samples in each group, data are shown as mean ± SEM, one-way ANOVA and Bonferroni’s multiple comparison test). F Enrichment of aggregated Tau and Aβ in the detergent-insoluble fractions of mouse brains and AD human cortex. Sarkosyl-insoluble fractions were blotted with antibodies against Aβ (4G8), or Tau T22 for Tau oligomers (representative of 3 mice). G immunogold EM showed the aggregated extracellular Aβ and intracellular AT8 in the hippocampus neurons of AD or HC humanized Abx-treated mice. Fibrils like structures (arrows) were highly increased in AD humanized Abx-treated mice (left panels, Scale bar: 200 nm). Quantitative analysis of Aβ and AT8 positive dots. (Right panel, n = 5 biologically independent samples in each group, data are shown as mean ± SEM, one-way ANOVA and Bonferroni’s multiple comparison test).