LTP and memory impairment caused by extracellular Aβ and Tau oligomers is APP-dependent
- University of Catania, Italy
- Università Cattolica del Sacro Cuore, Italy
- Columbia University, United States
- University of Toronto, Canada
- Albert Einstein College of Medicine, United States
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 Aβ and/or Tau.
Article and author information
Author details
Funding
National Institutes of Health (R01AG049402)
- Ottavio Arancio
Italian FFO
- Daniela PUZZO
Canadian Institutes of Health Research
- Paul Fraser
Catholic University Intramural Funds
- Claudio Grassi
Italian FFO
- Agostino Palmeri
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health and the European Community Council. All protocols involving animals were approved by Columbia University (#AC-AAAO5301), Università di Catania (#327/2013-B, #119-2017-PR), Università Cattolica del Sacro Cuore (#626-2016-PR), Albert Einstein College of Medicine (#20160407), and the respective Institutional Animal care and Use Committee (IACUC).
Copyright
© 2017, PUZZO et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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LTP and memory impairment caused by extracellular Aβ and Tau oligomers is APP-dependent
eLife 6:e26991.
https://doi.org/10.7554/eLife.26991
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