AD (Alzheimer's disease) is linked to Aβ (amyloid β-peptide) misfolding. Studies demonstrate that the level of soluble Aβ 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 Aβ oligomers or fibrils, suggesting that structural differences between these forms of Aβ exist. Using conditions which yield well-defined Aβ-(1–42) oligomers or fibrils, we studied the secondary structure of these species by ATR (attenuated total reflection)–FTIR (Fouriertransform infrared) spectroscopy. Whereas fibrillar Aβ was organized in a parallel β-sheet conformation, oligomeric Aβ displayed distinct spectral features, which were attributed to an antiparallel β-sheet structure. We also noted striking similarities between Aβ oligomers spectra and those of bacterial outer membrane porins. We discuss our results in terms of a possible organization of the antiparallel β-sheets in Aβ oligomers, which may be related to reported effects of these highly toxic species in the amyloid pathogenesis associated with AD.