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. 2023 Nov 3;14:7034. doi: 10.1038/s41467-023-42822-1

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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 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. 8 — a Schematic of the approach to generate APP knockout and isogenic control neurons. Created with BioRender.com. b Representative immunofluorescence images show increased ubiquitin (red) immunostaining in APP knockout neurons (MAP2, magenta), additionally stained for DAPI (blue), compared to controls. c Quantitative analysis shows significantly increased ubiquitin levels in APP knockout neurons compared to controls. Control n = 133, APP KO n = 151. p-value = 8.85E-09. d Immunostaining shows increased LC3B (arrow, red) immunostaining in APP knockout neurons (NeuN, magenta) compared to controls. e Quantitative analysis shows significantly increased LC3B levels in APP knockout neurons compared to controls. Control n = 17, APP KO n = 19. p-value = 3.86E-08. f Immunostaining shows decreased phospho-SMAD3 (red) immunostaining in APP knockout neurons (NeuN, magenta) compared to controls. g Quantitative analysis shows significantly decreased phospho-SMAD3 levels in APP knockout neurons compared to controls. Control n = 150, APP KO n = 156. p-value = 9.76E-11. ***p < 0.0001, two-tailed Student’s t-test. Data are represented as mean ± SEM. Cells from 3 independent differentiations of APP knockout and isogenic control cells were analyzed. Scale bars are 10 μm. Source data are provided as a Source Data file.