DHPC strongly affects the structure and oligomerization propensity of Alzheimer's Abeta(1-40) peptide.

摘要

Alzheimer's disease (AD) is thought to depend on the deleterious action of amyloid fibrils or oligomers derived from beta-amyloid (Abeta) peptide. Out of various known Abeta alloforms, the 40-residue peptide Abeta(1-40) occurs at highest concentrations inside the brains of AD patients. Its aggregation properties critically depend on lipids, and it was thus proposed that lipids could play a major role in AD. To better understand their possible effects on the structure of Abeta and on the ability of this peptide to form potentially detrimental amyloid structures, we here analyze the interactions between Abeta(1-40) and 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC). DHPC has served, due to its controlled properties, as a major model system for studying general lipid properties. Here, we show that DHPC concentrations of 8 mM or higher exert dramatic effects on the conformation of soluble Abeta(1-40) peptide and induce the formation of beta-sheet structure at high levels. By contrast, we find that DHPC concentrations well below the critical micelle concentration present no discernible effect on the conformation of soluble Abeta, although they substantially affect the peptide's oligomerization and fibrillation kinetics. These data imply that subtle lipid-peptide interactions suffice in controlling the overall aggregation properties and drastically accelerate, or delay, the fibrillation kinetics of Abeta peptide in near-physiological buffer solutions.