Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
Roberto Piacentini
Institute of Human Physiology, Università Cattolica del Sacro Cuore, Rome, Italy
Mauro Fá
Department of Pathology and Cell Biology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, United States
Walter Gulisano
Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
Domenica D Li Puma
Institute of Human Physiology, Università Cattolica del Sacro Cuore, Rome, Italy
Agnes Staniszewski
Department of Pathology and Cell Biology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, United States
Hong Zhang
Department of Pathology and Cell Biology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, United States
Maria Rosaria Tropea
Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
Sara Cocco
Institute of Human Physiology, Università Cattolica del Sacro Cuore, Rome, Italy
Agostino Palmeri
Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
Paul Fraser
Tanz Centre for Research in Neurodegenerative Diseases and Department of Medical Biophysics, University of Toronto, Toronto, Canada
Luciano D'Adamio
Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, United States
Department of Pathology and Cell Biology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New york, United States
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.
