Time-resolved infrared spectroscopy of pH-induced aggregation of the Alzheimer Abeta(1-28) peptide.

Aggregation of the Alzheimer's disease-related Abeta(1-28) peptide was induced by a rapid, sub-millisecond pH jump and monitored by time-resolved infrared spectroscopy on the millisecond to second time-scale. The release of protons was induced by the photolysis of a caged compound, 1-(2-nitrophenyl)ethyl sulfate (NPE-sulfate). The pH jump generated in our experimental setup is used to model the Abeta peptide structural conversions that may occur in the acidic endosomal/lysosomal cell compartment system. The aggregation of the Abeta(1-28) peptide induced by the pH jump from 8.5 to <6 yields an antiparallel beta-sheet structure. The kinetics of the structural transition is biphasic, showing an initial rapid phase with a transition from random coil to an oligomeric beta-sheet form with a time constant of 3.6 s. This phase is followed by a second slower transition, which yields larger aggregates during 48.0 s.