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.

Fa', M., Puzzo, D., Piacentini, R., Staniszewski, A., Zhang, H., Baltrons, M. A., Li Puma, D. D., Chatterjee, I., Li, J., Saeed, F., Berman, H., Ripoli, C., Gulisano, W., Gonzalez, J., Tian, H., Costa, J., Lopez, P., Davidowitz, E., Yu, W. H., Haroutunian, V., Brown, L., Palmeri, A., Sigurdsson, E., Duff, K., Teich, A. F., Honig, L., Sierks, M., Moe, J., D’adamio, L., Grassi, C., Kanaan, N., Fraser, P., Arancio, O., Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory, <<SCIENTIFIC REPORTS>>, 2016; (6): N/A-N/A. [doi:10.1038/srep19393] [http://hdl.handle.net/10807/71753]

Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory

Daniela; Piacentini;Maria Antonia; Li Puma;Hanna; Ripoli;Luciano; Grassi;
2016

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.
Inglese
Fa', M., Puzzo, D., Piacentini, R., Staniszewski, A., Zhang, H., Baltrons, M. A., Li Puma, D. D., Chatterjee, I., Li, J., Saeed, F., Berman, H., Ripoli, C., Gulisano, W., Gonzalez, J., Tian, H., Costa, J., Lopez, P., Davidowitz, E., Yu, W. H., Haroutunian, V., Brown, L., Palmeri, A., Sigurdsson, E., Duff, K., Teich, A. F., Honig, L., Sierks, M., Moe, J., D’adamio, L., Grassi, C., Kanaan, N., Fraser, P., Arancio, O., Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory, <<SCIENTIFIC REPORTS>>, 2016; (6): N/A-N/A. [doi:10.1038/srep19393] [http://hdl.handle.net/10807/71753]
File in questo prodotto:
File Dimensione Formato  
Sci. Rep. 6, 19393, 2016.pdf

accesso aperto

Tipologia file ?: Versione Editoriale (PDF)
Licenza: Creative commons
Dimensione 1.66 MB
Formato Adobe PDF
1.66 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/71753
Citazioni
  • ???jsp.display-item.citation.pmc??? 105
  • Scopus 168
  • ???jsp.display-item.citation.isi??? 167
social impact