LTP and memory impairment caused by extracellular Aβ and tau oligomers is APP- dependent

Daniela Puzzo, Roberto Piacentini, Mauro Fá, Walter Gulisano, Domenica D. Li Puma, Agnes Staniszewski, Hong Zhang, Maria Rosaria Tropea, Sara Cocco, Agostino Palmeri, Paul Fraser, Luciano D’Adamio, Claudio Grassi, Ottavio Arancio

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37 Scopus citations

Abstract

The concurrent application of subtoxic doses of soluble oligomeric forms of human amyloid-beta (oAβ) and Tau (oTau) proteins impairs memory and its electrophysiological surrogate long-term potentiation (LTP), effects that may be mediated by intra-neuronal oligomers uptake. Intrigued by these findings, we investigated whether oAβ and oTau share a common mechanism when they impair memory and LTP in mice. We found that as already shown for oAβ, also oTau can bind to amyloid precursor protein (APP). Moreover, efficient intra-neuronal uptake of oAβ and oTau requires expression of APP. Finally, the toxic effect of both extracellular oAβ and oTau on memory and LTP is dependent upon APP since APP-KO mice were resistant to oAβ- and oTau-induced defects in spatial/associative memory and LTP. Thus, APP might serve as a common therapeutic target against Alzheimer’s Disease (AD) and a host of other neurodegenerative diseases characterized by abnormal levels of Ab and/or Tau.

Original languageEnglish (US)
Article numbere26991
JournaleLife
Volume6
DOIs
StatePublished - Jul 11 2017

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ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Puzzo, D., Piacentini, R., Fá, M., Gulisano, W., Li Puma, D. D., Staniszewski, A., Zhang, H., Tropea, M. R., Cocco, S., Palmeri, A., Fraser, P., D’Adamio, L., Grassi, C., & Arancio, O. (2017). LTP and memory impairment caused by extracellular Aβ and tau oligomers is APP- dependent. eLife, 6, [e26991]. https://doi.org/10.7554/eLife.26991.001