Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory

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Abstract

Non-fibrillar soluble oligomeric forms of amyloid-β peptide (oAβ) and tau proteins are likely to play a major role in Alzheimer's disease (AD). The prevailing hypothesis on the disease etiopathogenesis is that oAβ initiates tau pathology that slowly spreads throughout the medial temporal cortex and neocortices independently of Aβ, 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 oAβ levels. The impairment is immediate as it raises as soon as 20 min 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 oAβ 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 Aβ on memory loss, offering new therapeutic opportunities in the therapy of AD and other neurodegenerative diseases associated with Aβ and tau pathology.

Original languageEnglish (US)
Article number19393
JournalScientific reports
Volume6
DOIs
StatePublished - Jan 20 2016

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Fá, M., Puzzo, D., Piacentini, R., Staniszewski, A., Zhang, H., Baltrons, M. A., Li Puma, D. D., Chatterjee, I., Li, J., Saeed, F., Berman, H. L., Ripoli, C., Gulisano, W., Gonzalez, J., Tian, H., Costa, J. A., Lopez, P., Davidowitz, E., Yu, W. H., ... Arancio, O. (2016). Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory. Scientific reports, 6, [19393]. https://doi.org/10.1038/srep19393