Antiparallel β-sheet: a signature structure of the oligomeric amyloid β-peptide

AD (Alzheimer's disease) is linked to A beta (amyloid beta-peptide) misfolding. Studies demonstrate that the level Of Soluble A beta oligomeric forms correlates better with the progression of the disease than the level of fibrillar forms. Conformation-dependent antibodies have been developed to detect either A beta oligomers or fibrils, suggesting that structural differences between these forms of At exist. Using conditions which yield well-defined A beta (1-42) oligomers or fibrils, We studied the secondary structure of these species by ATR (attenuated total reflection)-FTIR (Fourier-transform infrared) spectroscopy. Whereas fibrillar A beta was organized in a parallel beta-sheet conformation, oligomeric A beta displayed distinct spectral features, which were attributed to an antiparallel beta-sheet structure. We also noted striking similarities between A beta oligomers spectra and those of bacterial outer membrane porins. We discuss our results in terms of a possible organization of the antiparallel beta-sheets in A beta oligomers, which may be related to reported effects of these highly toxic species in the amyloid pathogenesis associated with AD.