In Alzheimer's disease, amyloid-β (Aβ) plaques and tau neurofibrillary tangles are the two pathological hallmarks. The co-occurrence and combined reciprocal pathological effects of Aβ and tau protein aggregation have been observed in animal models of the disease. However, the molecular mechanism of their interaction remain unknown. Using a variety of biophysical measurements, we here show that the native full-length tau protein solubilizes the Aβ40 peptide and prevents its fibrillation. The tau protein delays the amyloid fibrillation of the Aβ40 peptide at substoichiometric ratios, showing different binding affinities toward the different stages of the aggregated Aβ40 peptides. The Aβ monomer structure remains random coil in the presence of tau, as observed by nuclear magnetic resonance (NMR), circular dichroism (CD) spectroscopy and photoinduced cross-linking methods. We propose a potential interaction mechanism for the influence of tau on Aβ fibrillation.