A high-throughput conditioned-media-based screening system identifies inhibitors of aggregation induced by iPSC-secreted amyloid β

Abstract

Abstract In early drug discovery, in vitro screening is frequently used, but selected candidates often fail in vivo. Induced pluripotent stem cell (iPSC)–based disease models offer improved physiological relevance; however, the high costs of media and differentiation procedures limit large-scale testing. Here, we develop a high-throughput conditioned-media-based screening system—the High-throughput screening technology for Aggregation Inhibitors of Diseased cell-derived Aggregative Proteins (HaiDap) system—to identify inhibitors of aggregation induced by iPSC-secreted amyloid β (Aβ). Using conditioned media derived from differentiated iPSCs of a male Alzheimer’s disease patient, we screen extracts from 22 edible plants. Whereas PBS-based assays showed 40.9% (9/22) apparent selectivity, the HaiDap system demonstrates higher specificity (13.6%; 3/22). All three identified extracts ( O. aristatus , S. aromaticum , and G. yesoense ) significantly delay Aβ aggregation on neuronal surfaces in an iPSC-based assay. These findings suggest that the HaiDap system enables efficient, accurate, and low-cost screening of amyloid aggregation inhibitors.