The interaction of amyloid beta (Abeta) 25-35 with tau protein and with the peptide 1/2R (KVTSKCGSLGNIHHKPGGG), has been investigated by chromatography, electron microscopy, and surface plasmon resonance (SPR). Abeta 25-35 comprises the minimum region of Abeta peptide that is able to aggregate into fibrils, and 1/2R contains residues 307-325 from the tau region involved in microtubule binding. The results of chromatography showed that Abeta 25-35 induces the aggregation of tau protein and of tau peptide 1/2R. Likewise, the results of electron microscopy showed that Abeta 25-35 increases the tau peptide polymerization observed in the presence of polyanions like heparin. A decrease in Abeta 25-35 aggregation induced by tau peptide was also observed by both techniques. No direct interaction between tau protein immobilized on the sensor surface and Abeta 25-35 could be detected by SPR. However, incubation of tau protein at room temperature produced the loss of capability of this protein for interacting with the active biosensor surface. The presence of Abeta 25-35 during the incubation of tau protein makes more efficient this loss of interacting capability with the sensor surface. These results clearly indicate that Abeta 25-35, the peptide region to which the cytotoxic properties of Abeta can be assigned, interacts with the peptide region of tau protein involved in microtubule binding. This interaction produces the aggregation of tau peptide and the concomitant disassembling of Abeta 25-35, offering thus an explanation to the lack of co-localization of neurofibrillary tangles and senile plaques in Alzheimer's disease, and suggesting the possibility that tau protein may have a protective action by preventing Abeta from adopting the cytotoxic, aggregated form.