A growing amount of evidence indicates the involvement of extracellular matrix components, especially laminins, in the development of Alzheimer's disease, although their role remains unclear. In this study, we clearly demonstrate that laminin 1 inhibits -amyloid peptide (A)-induced neuronal cell death by preventing the fibril formation and interaction of the A peptide with cell membranes. The presence of laminin at a laminin/A peptide molar ratio of 1:800 significantly inhibits the A-induced apoptotic events, together with inhibition of amyloid fibril formation. The inhibitory effects of laminin 1 were time- and dose-dependent, whereas laminin 2 had less effect on A neurotoxicity. A preincubation of laminin and A was not required to observe the protective effect of laminin, suggesting a direct interaction between laminin 1 and A. Moreover, laminin had no effect on the toxicity of the fibrillar A peptide, suggesting an interaction of laminin with nonfibrillar species of the A peptide, sequestering the peptide in a soluble form. These data extend our understanding of laminin-dependent binding of A and highlight the possible modulation role of laminin regarding A aggregation and neurotoxicity in vivo.