A beta peptides aggregate to form insoluble and neurotoxic fibrils associated with Alzheimer's disease. Inhibition of the aggregation has been the subject of numerous studies. Here we describe a novel, substoichiometric inhibitor of A beta(1-40) fibrillization as a tandem dimeric construct consisting of A beta(40-1) (reverse sequence) linked to A beta(1-40) via an eight residue glycine linker. At molar ratios of the tandem peptide to A beta(1-40) of 1:10 to 1:25 inhibition of fibrillization, as measured by ThioflavinT, was observed. We postulate that the tandem construct binds to a fibrillar intermediate but the reverse sequence delays or prevents further monomer association. (C) 2010 Elsevier Inc. All rights reserved.