Amyloid β Peptide Modifies Membrane Architecture and Surface Electrostatic Properties of Human Red Blood Cells.

Abnormal accumulation of amyloid-beta (Aβ) peptides in the brain is a hallmark of Alzheimer's disease (AD). Importantly, the peripheral blood cells are also exposed to the effects of pathological peptides that accumulate in AD. Herein, the interaction of Aβ42 oligomers (Aβ42) with human red blood cells (RBCs) and erythrocyte ghosts as in vitro models for AD is studied combining fluorescence spectroscopy, fluorescence microscopy, and electrokinetics. The binding of Aβ42 to RBCs was evidenced by the use of a fluorescent-labeled peptide. The membrane lipid order increased with the increase in both the Aβ42 concentration and the incubation time, creating a lipid-protein microenvironment characterized by higher molecular order and reduced heterogeneity in RBC membranes compared to control conditions. Notably, the increase in lipid order was less pronounced in erythrocyte ghosts than in intact RBCs. Furthermore, the ζ-potential measurements revealed Aβ42 induced alteration of the surface potential of RBCs in a concentration- and time-dependent manner, with freshly isolated RBCs exhibiting a highly negative potential that became increasingly negative at higher Aβ42 concentrations. These findings suggest that Aβ42 not only impacts neuronal function but also significantly alters the physical properties of RBCs that might compromise their function, potentially contributing to the systemic effects observed in AD.