Time-Dependent Lipid Dynamics, Organization and Peptide-Lipid Interaction in Phospholipid Bilayers with Incorporated β-Amyloid Oligomers.

Nonfibrillar β-amyloid (Aβ) oligomers are considered as major neurotoxic species in the pathology of Alzheimer's disease. The presence of Aβ oligomers was shown to cause membrane disruptions in a broad range of model systems. However, the molecular basis of such a disruption process remains unknown.

Model Phospholipid Liposomes to Study the β-Amyloid-Peptide-Induced Membrane Disruption.

Model phospholipid liposomes have been utilized widely to study the molecular interactions between peptides and membrane bilayers. In the mechanistic study of Alzheimer's disease (AD), disruption of neuronal cell membranes has been considered as a major contribution for the β-amyloid (Aβ) peptides' neurotoxicity. However, clear interpretation of the Aβ-induced cellular membrane at high-resolution level is challenging because of the co-existence of multiple pathways.

The on-fibrillation-pathway membrane content leakage and off-fibrillation-pathway lipid mixing induced by 40-residue β-amyloid peptides in biologically relevant model liposomes.

Disruption of the synaptic plasma membrane (SPM) induced by the aggregation of β-amyloid (Aβ) peptides has been considered as a potential mechanism for the neurotoxicity of Aβ in Alzheimer's disease (AD). However, the molecular basis of such membrane disruption process remains unclear, mainly because of the severe systematic heterogeneity problem that prevents the high-resolution studies. Our previous studies using a two-component phosphatidylcholine (PC)/phosphatidylglycerol (PG) model liposome showed the presence of Aβ-induced membrane disruptions that were either on the pathway or off the pathway of fibril formation.