Using interfacial rheology to understand the mechanism of Alzheimer’s disease

In Alzheimer's disease, amyloid plaques and, predominantly, extracellular Amyloid-beta (A-beta) oligomers are important byomarkers associated with neuronal cells loss and dysfunction. Some experiments in the literature demonstrates that A-beta peptides induce significative changes in membrane organization, reducing stiffness and ultimately forming pores that contribute to the damage and death of neuronal cells. Understanding the interaction between A-beta and neuronal lipid membranes is crucial for the study of Alzheimer’s disease and drug development. This work aims to quantify the interactions, binding mechanisms and insertion of A-beta peptides into lipid membranes, using interfacial rheology and microscopy techniques. Initially, we used a Langmuir trough to measure the surface pressure at the interface of a model lipid layer (DPPC) at the air-water interface. Shear interfacial rheology employing a double wall ring was also used to obtain the surface viscosity, while cryo-SEM visualizations are performed to examine the microstructure of the compounds and interfaces formed. Upon introducing A-beta into the water phase system, a decrease in surface pressure, and a weekening effect on interfacial viscosity were observed. The study includes experiments with varying concentrations of A-beta and different temperatures. Additionally, we investigate the effect of a novel organic compound at the interface to assess its potential for restoring the mechanical properties of the interface.