Jong-Chan Park^1,2,3,4,11, So-Yeong Jang^5,11, Dongjoon Lee^1,3,11, Jeongha Lee¹, Uiryong Kang⁵, Hongjun Chang⁵, Haeng Jun Kim^1,3, Sun-Ho Han^1,2,3, Jinsoo Seo⁶, Murim Choi¹, Dong Young Lee^7,8,9, Min Soo Byun¹⁰, Dahyun Yi⁷, Kwang-Hyun Cho^5,* & Inhee Mook-Jung^1,2,3,*

¹Department of Biochemistry and Biomedical Sciences, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea.
²Neuroscience Research Institute, Medical Research Center, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea.
³SNU Dementia Research Center, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea.
⁴Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, United Kingdom.
⁵Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.
⁶Department of Brain and Cognitive Science, Daegu Gyeongbuk Institute of Sciences and Technology (DGIST), Daegu 42988, Republic of Korea.
⁷Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Seoul 03080, Republic of Korea.
⁸Department of Psychiatry, College of medicine, Seoul National University, Seoul 03080, Republic of Korea.
⁹Department of Neuropsychiatry, Seoul National University Hospital, Seoul 03080, Republic of Korea.
¹⁰Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea.

¹¹These authors contributed equally: Jong-Chan Park, So-Yeong Jang, Dongjoon Lee.

^*Corresponding author

Developing effective drugs for Alzheimer’s disease (AD), the most common cause of dementia, has been difficult because of complicated pathogenesis. Here, we report an efficient, network-based drug-screening platform developed by integrating mathematical modeling and the pathological features of AD with human iPSC-derived cerebral organoids (iCOs), including CRISPR-Cas9-edited isogenic lines. We use 1300 organoids from 11 participants to build a high-content screening (HCS) system and test blood–brain barrier-permeable FDA-approved drugs. Our study provides a strategy for precision medicine through the convergence of mathematical modeling and a miniature pathological brain model using iCOs.