title: DHPC strongly affects the structure and oligomerization propensity of Alzheimer's Aβ(1-40) peptide.
abstract: Alzheimer's disease (AD) is thought to depend on the deleterious action of amyloid fibrils or oligomers derived from β-amyloid (Aβ) peptide. Out of various known Aβ alloforms, the 40-residue peptide Aβ(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 Aβ and on the ability of this peptide to form potentially detrimental amyloid structures, we here analyze the interactions between Aβ(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 Aβ(1-40) peptide and induce the formation of β-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 Aβ, 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 Aβ peptide in near-physiological buffer solutions.
authors.affiliation: Department of Pharmaceutical Technology, Friedrich-Schiller-University Jena, 07743 Jena, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Dahse
authors.forename: Megan
authors.initials: M
authors.lastname: Garvey
authors.forename: Michael
authors.initials: M
authors.lastname: Kovermann
authors.forename: Alexander
authors.initials: A
authors.lastname: Vogel
authors.forename: Jochen
authors.initials: J
authors.lastname: Balbach
authors.forename: Marcus
authors.initials: M
authors.lastname: Fändrich
authors.forename: Alfred
authors.initials: A
authors.lastname: Fahr
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure; D055592:Biophysical Phenomena; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure; D010742:Phospholipid Ethers / Q000737:chemistry*; D011487:Protein Conformation; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013500:Surface Tension
chemical_list: C052298:1,2-dihexadecyl-sn-glycero-3-phosphocholine; D016229:Amyloid beta-Peptides; D008823:Micelles; D010446:Peptide Fragments; D010742:Phospholipid Ethers; C078592:amyloid beta-protein (1-40)