Size-Dependent Interaction of Amyloid β Oligomers with Brain Total Lipid Extract Bilayer-Fibrillation Versus Membrane Destruction.

Abstract

Amyloid β, Aβ(1-42), is a component of senile plaques present in the brain of Alzheimer's disease patients and one of the main suspects responsible for pathological consequences of the disease. Herein, we directly visualize the Aβ activity toward a brain-like model membrane and demonstrate that this activity strongly depends on the Aβ oligomer size. PeakForce quantitative nanomechanical mapping mode of atomic force microscopy imaging revealed that the interaction of large-size (LS) Aβ oligomers, corresponding to high-molecular-weight Aβ oligomers, with the brain total lipid extract (BTLE) membrane resulted in accelerated Aβ fibrillogenesis on the membrane surface. Importantly, the fibrillogenesis did not affect integrity of the membrane. In contrast, small-size (SS) Aβ oligomers, corresponding to low-molecular-weight Aβ oligomers, created pores and then disintegrated the BTLE membrane. Both forms of the Aβ oligomers changed nanomechanical properties of the membrane by decreasing its Young's modulus by ∼45%. Our results demonstrated that both forms of Aβ oligomers induce the neurotoxic effect on the brain cells but their action toward the membrane differs significantly.