Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory

M. Fá, D. Puzzo, R. Piacentini, A. Staniszewski, H. Zhang, M. A. Baltrons, D. D. Li Puma, I. Chatterjee, J. Li, F. Saeed, H. L. Berman, C. Ripoli, W. Gulisano, J. Gonzalez, H. Tian, J. A. Costa, P. Lopez, E. Davidowitz, W. H. Yu, V. Haroutunian & 13 others L. M. Brown, A. Palmeri, E. M. Sigurdsson, K. E. Duff, A. F. Teich, L. S. Honig, M. Sierks, J. G. Moe, L. D'Adamio, C. Grassi, N. M. Kanaan, P. E. Fraser, O. Arancio

Research output: Contribution to journalArticle

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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
Article number19393
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Jan 20 2016

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Long-Term Memory
Long-Term Potentiation
Alzheimer Disease
Memory Disorders
Pathology
tau Proteins
Peptides
Poisons
Neocortex
Temporal Lobe
Amyloid
Neurodegenerative Diseases
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Fá, M., Puzzo, D., Piacentini, R., Staniszewski, A., Zhang, H., Baltrons, M. A., ... Arancio, O. (2016). Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory. Scientific Reports, 6, [19393]. https://doi.org/10.1038/srep19393

Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory. / 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.; Haroutunian, V.; Brown, L. M.; Palmeri, A.; Sigurdsson, E. M.; Duff, K. E.; Teich, A. F.; Honig, L. S.; Sierks, M.; Moe, J. G.; D'Adamio, L.; Grassi, C.; Kanaan, N. M.; Fraser, P. E.; Arancio, O.

In: Scientific Reports, Vol. 6, 19393, 20.01.2016.

Research output: Contribution to journalArticle

Fá, M, Puzzo, D, Piacentini, R, Staniszewski, A, Zhang, H, Baltrons, MA, Li Puma, DD, Chatterjee, I, Li, J, Saeed, F, Berman, HL, Ripoli, C, Gulisano, W, Gonzalez, J, Tian, H, Costa, JA, Lopez, P, Davidowitz, E, Yu, WH, Haroutunian, V, Brown, LM, Palmeri, A, Sigurdsson, EM, Duff, KE, Teich, AF, Honig, LS, Sierks, M, Moe, JG, D'Adamio, L, Grassi, C, Kanaan, NM, Fraser, PE & Arancio, O 2016, 'Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory', Scientific Reports, vol. 6, 19393. https://doi.org/10.1038/srep19393
Fá M, Puzzo D, Piacentini R, Staniszewski A, Zhang H, Baltrons MA et al. Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory. Scientific Reports. 2016 Jan 20;6. 19393. https://doi.org/10.1038/srep19393
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. ; Haroutunian, V. ; Brown, L. M. ; Palmeri, A. ; Sigurdsson, E. M. ; Duff, K. E. ; Teich, A. F. ; Honig, L. S. ; Sierks, M. ; Moe, J. G. ; D'Adamio, L. ; Grassi, C. ; Kanaan, N. M. ; Fraser, P. E. ; Arancio, O. / Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory. In: Scientific Reports. 2016 ; Vol. 6.
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