Charge Modification of Lysine Mitigates Amyloid-β Aggregation

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative condition characterized by the deposition of amyloid-beta (A beta) peptides, which aggregate into toxic structures such as oligomers, fibrils, and plaques. The presence of these A beta aggregates in the brain plays a crucial role in the pathophysiology, leading to synaptic dysfunction and cognitive impairment. Understanding how physiological factors affect A beta aggregation is essential, and therefore, exploring their influence in vitro will likely provide insights into their role in AD pathology. In this study, we investigated the effects of physiological, free amino acids on A beta aggregation dynamics. We focused on positively charged amino acids, particularly lysine, and employed a chemical modification, methylation, to neutralize its charge. Our analyses revealed that modified lysine significantly reduced A beta aggregation, indicating that charge distribution of amino acids plays a crucial role in modulating A beta aggregation behavior. These findings enhance our understanding of the regulatory factors influencing A beta aggregation and highlight important considerations for future research on A beta.