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. 2021 Jan 12;12:280. doi: 10.1038/s41467-020-20440-5

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© The Author(s) 2021

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 — To establish drug assessment platform for Alzheimer’s disease (AD), three steps were performed: (i) Generation of iPSC-derived organoids (iCOs) both from normal and sporadic AD (sAD) participants, and CRISPR-Cas9 ApoE4 isogenic lines were used. (ii) Systems biology-based AD pathway simulation; Signaling network construction, network model validation, and identification of control nodes steps were conducted. (iii) Validation of drugs from the simulation; FDA-approved drugs were used, and the degree of AD pathogenesis was quantified by the high-contents screening (HCS) imaging system. Approximately, 1300 organoids from 11 participants were used for the drug assessment platform. PiB Pittsburgh compound B, ApoE apolipoprotein E, ELISA enzyme-linked immunosorbent assay, Aβ beta-amyloid, p-tau phosphorylated tau.