Amyloid-beta (A beta) peptides can exist in distinct forms including monomers, oligomers and fibrils, consisting of increased numbers of monomeric units. Among these, A beta oligomers are implicated as the primary toxic species as pointed by multiple lines of evidence. It has been suggested that toxicity could be rendered by the soluble higher-molecular-weight (high-n) A beta oligomers. Yet, the most culpable form in the pathogenesis of Alzheimer's disease (AD) remains elusive. Moreover, the potential interaction among the insoluble fibrils that have been excluded from the responsible aggregates in AD development, A beta monomers and high-n oligomers is undetermined. Here, we report that insoluble A beta fibrillar seeds can interact with A beta monomers at the stoichiometry of 1:2 (namely, each A beta molecule of seed can bind to two A beta monomers at a time) facilitating the fibrillization by omitting the otherwise mandatory formation of the toxic high-n oligomers during the fibril maturation. As a result, the addition of exogenous A beta fibrillar seeds is seen to rescue neuronal cells from A beta cytotoxicity presumably exerted by high-n oligomers, suggesting an unexpected protective role of A beta fibrillar seeds. (C) 2013 Elsevier Inc. All rights reserved.