Non-fibrillar soluble oligomeric forms of amyloid-\u3b2 peptide (oA\u3b2) and tau proteins are likely to play a major role in Alzheimer's disease (AD). The prevailing hypothesis on the disease etiopathogenesis is that oA\u3b2 initiates tau pathology that slowly spreads throughout the medial temporal cortex and neocortices independently of A\u3b2, eventually leading to memory loss. Here we show that a brief exposure to extracellular recombinant human tau oligomers (oTau), but not monomers, produces an impairment of long-term potentiation (LTP) and memory, independent of the presence of high oA\u3b2 levels. The impairment is immediate as it raises as soon as 20\u2009min after exposure to the oligomers. These effects are reproduced either by oTau extracted from AD human specimens, or naturally produced in mice overexpressing human tau. Finally, we found that oTau could also act in combination with oA\u3b2 to produce these effects, as sub-toxic doses of the two peptides combined lead to LTP and memory impairment. These findings provide a novel view of the effects of tau and A\u3b2 on memory loss, offering new therapeutic opportunities in the therapy of AD and other neurodegenerative diseases associated with A\u3b2 and tau pathology
