A logical network-based drug-screening platform for Alzheimer's disease representing pathological features of human brain organoids

Nat Commun. 2021 Jan 12;12(1):280. doi: 10.1038/s41467-020-20440-5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology*
  • Brain / pathology*
  • Cinnamates / pharmacology
  • Cinnamates / therapeutic use
  • Drug Evaluation, Preclinical*
  • Gene Regulatory Networks* / drug effects
  • High-Throughput Screening Assays
  • Humans
  • Induced Pluripotent Stem Cells / metabolism
  • Models, Biological
  • Organoids / pathology*
  • Reproducibility of Results
  • Risk Factors


  • Cinnamates
  • ethyl cinnamate