Probing pH effects on oligomerization of Alzheimer's amyloid-ß peptide by single-molecule spectroscopy

CHED 1020

Kyle Dukes, Dukesk2@winthrop.edu, Cassie Rodenberg, and Robin Lammi, lammir@winthrop.edu. Department of Chemistry, Physics, and Geology, Winthrop University, 101 Sims Science Building, Rock Hill, SC 29733
Misfolding and aggregation of amyloid-ß peptide (Aß) are recognized as causative events in Alzheimer's disease. Contrary to earlier hypotheses, recent results suggest that small, soluble oligomers are the pathogenic agents; therefore, detailed examination of the earliest peptide-association steps is crucial to a molecular-level understanding of Alzheimer's disease. We have utilized single-molecule spectroscopy to monitor oligomer formation in surface-tethered, fluorescently labeled Aß(1-40) peptides under neutral and acidic conditions. Fresh samples at pH 7.4 consist primarily of monomers and dimers, with a small percentage of trimers; after ageing for five days, the proportions of dimers and trimers are slightly increased. At pH 5.8, peptide association is rapid: fresh samples are dominated by trimers and tetramers, with fewer dimers and larger species. Oligomer formation is successfully inhibited by the known ß-sheet-breaker peptide iAß5, suggesting that some degree of ß-sheet structure is present in very small aggregates. Detailed conformational studies are underway.