Experimental Evidence for the Reorganization of β-Strands within Aggregates of the Aβ(16−22) Peptide

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Abstract
Amyloidogenic deposits that accumulate in brain tissue with the progression of Alzheimer's disease contain large amounts of the amyloid β-peptide. A small fragment of this peptide, comprising residues 16−22 (Aβ(16−22)), forms β-sheets in isolation, which then aggregate into amyloid fibrils. Here, using isotope edited infrared spectroscopy to probe the secondary structure of the peptide with residue level specificity, we are able to show conclusively that the β-sheets formed are antiparallel and, following an anneal cycle or prolonged incubation, are in register with the central residue (Phe19) in alignment across all strands. The alignment of strands proceeds via a rapid interchange from one sheet to another. This realignment of the peptide strands into a more favorable registry may have important implications for therapeutics since previous work has shown that well aligned β-sheets form more stable amyloid fibrils.