The amyloid-beta (A beta) 42 oligomers are much more toxic than A beta 40 oligomers in Alzheimer's disease. Numerous experiments indicate that toxicity could involve the formation of pores in membranes, but experimental high-resolution structure determination of these pore-forming A beta oligomers has been impeded by aggregate heterogeneity. Using extensive atomistic simulations, low-resolution data obtained in lipid bilayers, and other theoretical factors, we proposed atomic structures of A beta 40 and A beta 42 beta-barrels in a bilayer mimicking a neuronal membrane. The 3D model, which consists of tetramer subunits, two distinct beta hairpin motifs and an asymmetric arrangement of eight antiparallel beta-strands, is drastically destabilized for A beta 40 compared to its A beta 42 counterpart. Our computational modeling has several implications in Alzheimer's disease, sheds light on the amyloid pore hypothesis, and explains the higher deleterious property of A beta 42.