Atomic Force Microscopy Analysis of EPPS-Driven Degradation and Reformation of Amyloid-β Aggregates.

Amyloid-β (Aβ) peptides can be aggregated into β-sheet rich fibrils or plaques and deposited on the extracellular matrix of brain tissues, which is a hallmark of Alzheimer's disease. Several drug candidates have been designed to retard the progression of the neurodegenerative disorder or to eliminate toxic Aβ aggregates. Recently, 4-(2-Hydroxyethyl)-1-piperazinepropanesulfonic acid (EPPS) has emerged as a promising drug candidates for elimination of toxic Aβ aggregates. However, the effect of EPPS on the degradation of Aβ aggregates such as fibrils has not yet been fully elucidated. In this article, we investigate the EPPS-driven degradative behavior of Aβ aggregates at the molecular level by using high-resolution atomic force microscopy. We synthesized Aβ fibrils and observed degradation of fibrils following treatment with various concentrations (1-50 mM) of EPPS for various time periods. We found that degradation of Aβ fibrils by EPPS increased as a function of concentration and treatment duration. Intriguingly, we also found regeneration of Aβ aggregates with larger sizes than original aggregates at high concentrations (10 and 50 mM) of EPPS. This might be attributed to a shorter lag phase that facilitates reformation of Aβ aggregates in the absence of clearance system.