Alzheimers disease (AD) pathology is hypothesized to be triggered by amyloid beta-protein (A beta) assembly into oligomers. Oligomer size distributions of both predominant A beta alloforms, A beta(40) and A beta(42), can be determined in vitro using cross-linking followed by gel electrophoresis. Cross-linking, which can occur in vivo in the presence of copper and hydrogen peroxide, was recently shown to stabilize A beta oligomers by inhibiting their conversion into fibrils. Whereas several studies showed that cross-linking is facilitated by dityrosine bond formation, the molecular-level mechanism of cross-linking remains unclear. Here, we use efficient discrete molecular dynamics with DMD4B-HYDRA force field to examine the effect of cross-linking via tyrosines on A beta oligomer formation. Our results show that cross-linking via tyrosines promotes A beta self-assembly, in particular that of A beta(40), but does not account for cross-linked oligomers larger than A beta(40) trimers and A beta(42) tetramers. Cross-linking via tyrosines profoundly alters A beta(40) and A beta(42) oligomer conformations by increasing the solvent exposure of hydrophobic residues, resulting in elongated oligomeric morphologies that differ from globular structures of noncross-linked oligomers. When compared to available experimental data, our findings imply that amino acids other than tyrosines are involved in A beta cross-linking, a proposition that is currently under investigation.