The amyloid β peptide (Aβ) with 39-42 residues is the major component of amyloid plaques found in brains of Alzheimer's disease patients, and soluble oligomeric peptide aggregates mediate toxic effects on neurons. The Aβ aggregation involves a conformational change of the peptide structure to β-sheet. In the present study, we report on the effect of detergents on the structure transitions of Aβ, to mimic the effects that biomembranes may have. In vitro, monomeric Aβ(1-40) in a dilute aqueous solution is weakly structured. By gradually adding small amounts of sodium dodecyl sulfate (SDS) or lithium dodecyl sulfate to a dilute aqueous solution, Aβ(1-40) is converted to β-sheet, as observed by CD at 3 °C and 20 °C. The transition is mainly a two-state process, as revealed by approximately isodichroic points in the titrations. Aβ(1-40) loses almost all NMR signals at dodecyl sulfate concentrations giving rise to the optimal β-sheet content (approximate detergent/peptide ratio = 20). Under these conditions, thioflavin T fluorescence measurements indicate a maximum of aggregated amyloid-like structures. The loss of NMR signals suggests that these are also involved in intermediate chemical exchange. Transverse relaxation optimized spectroscopy NMR spectra indicate that the C-terminal residues are more dynamic than the others. By further addition of SDS or lithium dodecyl sulfate reaching concentrations close to the critical micellar concentration, CD, NMR and FTIR spectra show that the peptide rearranges to form a micelle-bound structure with α-helical segments, similar to the secondary structures formed when a high concentration of detergent is added directly to the peptide solution.
|Original language||American English|
|Number of pages||12|
|Publication status||Published - Oct 2008|
- Amyloid β peptide