BPS2026 – Exploring amyloid-beta interactions in the context of calcification-related diseases

Age-related macular degeneration (AMD) is the leading cause of vision loss in aging populations, significantly impacting the quality of life. The condition is characterized by small extracellular deposits that accumulate in the retina named drusen. Drusen are composed of a lipid core, a mineral layer of calcium-based hydroxyapatite (HAP), and a protein-coated surface. Amyloid beta (A-β) has been found in the protein layer of drusen and is also widely known to be associated with Alzheimer’s disease where it forms cytotoxic fibrils. However, its role in AMD and its interactions with the minerals in drusen during the mineralization process is largely unknown. Therefore, this project aims to explore how A-β interacts with hydroxyapatite and whether these interactions lead to A-β aggregation. Here, we show how A-β aggregation kinetics are modulated in the presence of hydroxyapatite and different mineral phases using ThT kinetic assays. In addition, electron and fluorescence microscopy methods were used to characterize the deposits formed from kinetic assays. To enable these experiments, an optimized protocol was developed for the recombinant expression and purification of highly pure and monomeric A-β. These experiments provide insights into the interactions between A-β and calcification in diseases such as AMD.