ethyl-cinnamate and Alzheimer-Disease

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.

Topics: Alzheimer Disease; Brain; Cinnamates; Drug Evaluation, Preclinical; Gene Regulatory Networks; High-Throughput Screening Assays; Humans; Induced Pluripotent Stem Cells; Models, Biological; Organoids; Reproducibility of Results; Risk Factors