Amyloid capture and aggregation inhibition by human serum albumin

Abstract

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by amyloid-beta (Aβ) aggregation, primarily involving the peptides Aβ40 and Aβ42. Human serum albumin (HSA) has emerged as a potential therapeutic agent due to its ability to bind Aβ, inhibit aggregation, and promote disaggregation. This study quantitatively examined the interactions of HSA with both monomeric and aggregated forms of Aβ40 and Aβ42 using fluorescence techniques, including bulk steady-state fluorescence, fluorescence anisotropy, time-resolved fluorescence, and Fluorescence Correlation Spectroscopy (FCS). The binding constants determined from these methods were 4.45 × 104 M−1 for Aβ42 and 1.8 × 104 M−1 for Aβ40, indicating strong but differential affinities. FCS demonstrated that HSA effectively dissociates Aβ aggregates, shifting the equilibrium toward monomeric states, with the disaggregation capacity positively correlated with HSA concentration. These findings support HSA's utility in therapies like plasma exchange to reduce the cerebral Aβ burden, providing critical insights into its mechanistic role and therapeutic potential.