Alzheimer's disease (AD), the leading cause of dementia among the elderly, currently affects 4.5 million Americans. In individuals with AD, atypical changes in nerve cells cause many connections in the brain to be disrupted. One factor believed to contribute to the onset of AD is the abnormal folding of the amyloid-b protein (Ab). Although Ab initially exists as a monomer, misfolding of the monomeric Ab peptide into amyloid fibrils leads to the deposition of amyloid plaques, the characteristic pathology of AD brain. It has been shown that monomeric Ab is inert, but it is unknown which form of Ab aggregate is the primary toxic species. The toxic species could be either the soluble intermediate protofibrils or the insoluble mature fibrils. A number of cell receptors are capable of binding Ab. One step towards determining the active Ab species is to identify which form of Ab is most capable of interacting with cells. We initiated these investigations by examining the a₅b₁ integrin, expressed by a variety of cells, including neurons. An enzyme-linked immunosorbent assay (ELISA) was employed to examine the differences in binding affinities among various assembly forms of Ab and the a₅b₁ integrin. All dissociation constants were in the nanomolar range, suggesting that all Ab species readily bind to the a₅b₁ integrin. In addition, monomeric and fibrillar Ab had the highest binding affinities, while the intermediate protofibril had the smallest. These results fail to correlate with species toxicity and indicate that other factors, such as subsequent signaling events, must contribute to Ab activity.