The role of zinc, an essential element for normal brain function, in the pathology of Alzheimer's disease (AD) is poorly understood. On one hand, physiological and genetic evidence from transgenic mouse models supports its pathogenic role in promoting the deposition of the amyloid beta-protein (A beta) in senile plaques. On the other hand, levels of extracellular ("free") zinc in the brain, as inferred by the levels of zinc in cerebrospinal fluid, were found to be too low for inducing A beta aggregation. Remarkably, the release of transient high local concentrations of zinc during rapid synaptic events was reported. The role of such free zinc pulses in promoting A beta aggregation has never been established. Using a range of time-resolved structural and spectroscopic techniques, we found that zinc, when introduced in millisecond pulses of micromolar concentrations, immediately interacts with A beta 1-40 and promotes its aggregation. These interactions specifically stabilize non-fibrillar pathogenic related aggregate forms and prevent the formation of A beta fibrils (more benign species) presumably by interfering with the self-assembly process of A beta. These in vitro results strongly suggest a significant role for zinc pulses in A beta pathology. We further propose that by interfering with A beta self-assembly, which leads to insoluble, non-pathological fibrillar forms, zinc stabilizes transient, harmful amyloid forms. This report argues that zinc represents a class of molecular pathogens that effectively perturb the self-assembly of benign A beta fibrils, and stabilize harmful non-fibrillar forms.