Cross-Category Screening of Food Samples for Amyloid-β42 Aggregation-Inhibitory Activity Using a Microliter-Scale...

Alzheimer's disease (AD) is associated with the aggregation and deposition of amyloid-β (Aβ), making Aβ aggregation an important target in AD-related research. Food-derived components have attracted attention as potential modulators of Aβ-related processes, but the direct effects of diverse food samples on Aβ42 aggregation remain unclear. Here, we screened 120 food-sample preparations derived from 115 food items for inhibitory activity against Aβ42 aggregation using an automated microliter-scale high-throughput screening system with quantum-dot-labeled Aβ (QDAβ). Among primary screening samples, 34 showed detectable Aβ42 aggregation-inhibitory activity, and 12 were classified as highly active (1/EC₅₀ ≥ 10 mL/mg). Within the present screening set, highly active samples were frequently observed among tea-related samples. Black tea, Camembert, Red perilla, and Black soybean were selected as representative hits for further validation. Automated MSHTS images and dose-response data showed concentration-dependent suppression of Aβ42 aggregate formation. These inhibitory effects were further supported by thioflavin T (ThT) assays and transmission electron microscopy, which showed suppression of ThT-positive fibrillar aggregation and reduced fibrillar aggregate formation. In differentiated PC12 cells, selected food samples increased cell viability in Aβ42-treated cells at some concentrations. These findings provide a basis for functional food research and active component analysis of food-derived Aβ42 aggregation modulators.