Time-Resolved Infrared Spectroscopy of pH-Induced Aggregation of the Alzheimer Aβ1-28 Peptide

Alex Perálvarez-Marín*, Andreas Barth, Astrid Gräslund

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

52 Citations (Scopus)

Abstract

Aggregation of the Alzheimer's disease-related Aβ1-28 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 Aβ peptide structural conversions that may occur in the acidic endosomal/lysosomal cell compartment system. The aggregation of the Aβ1-28 peptide induced by the pH jump from 8.5 to < 6 yields an antiparallel β-sheet structure. The kinetics of the structural transition is biphasic, showing an initial rapid phase with a transition from random coil to an oligomeric β-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.

Original languageEnglish
Pages (from-to)589-596
Number of pages8
JournalJournal of Molecular Biology
Volume379
Issue number3
DOIs
Publication statusPublished - 6 Jun 2008

Keywords

  • Alzheimer's disease
  • amyloid
  • caged compounds
  • endosomal/lysosomal acidification
  • FTIR spectroscopy

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