Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory
Fà, Mauro (Columbia University. Department of Pathology and Cell Biology)
Puzzo, Daniela (University of Catania. Department of Biomedical and Biotechnological Sciences)
Piacentini, Roberto (Università Cattolica del Sacro Cuore. Institute of Human Physiology)
Staniszewski, A. (Columbia University. Department of Pathology)
Zhang, H. (Columbia University. Department of Pathology)
Baltrons Soler, Ma. Antonia (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Li Puma, Domenica Donatella (Università Cattolica del Sacro Cuore. Institute of Human Physiology)
Chatterjee, I. (Oligomerix)
Li, J. (Third Military Medical University. Department of Neurology)
Saeed, Faisal (Columbia University. Department of Pathology and Cell Biology)
Berman, Hanna (Columbia University. Department of Pathology)
Ripoli, Cristian (Università Cattolica del Sacro Cuore. Institute of Human Physiology)
Gulisano, Walter (University of Catania. Department of Biomedical and Biotechnological Sciences)
Gonzalez, Juana Benedí (Rockefeller University. Translational Technology Core Laboratory)
Tian, H. (Tempe. Department of Chemical Engineering)
Costa, J. A. (Columbia University. Department of Pathology and Cell Biology)
Lopez, Patricia (Oligomerix)
Davidowitz, Eliot J. (Oligomerix)
Yu, Wai Haung (Columbia University. Department of Pathology and Cell Biology)
Haroutunian, Vahram H. (The Mount Sinai School of Medicine. Department of Psychiatry)
Brown, Lewis M. (Columbia University. Department of Biological Sciences)
Palmeri, Agostino (University of Catania. Department of Biomedical and Biotechnological Sciences)
Sigurdsson, Einar (NYU Langone Medical Center. Department of Neuroscience and Physiology)
Duff, Karen E. (Columbia University. Department of Pathology and Cell Biology)
Teich, Andrew (Columbia University. Department of Pathology and Cell Biology)
Honig, Lawrence S. (Columbia University. Department of Pathology and Cell Biology)
Sierks, M. (Rockefeller University. Translational Technology Core Laboratory)
Moe, James G. (Oligomerix)
D'Adamio, Luciano (Einstein College of Medicine. Department of Microbiology and Immunology)
Grassi, Claudio (Hospitalization and Health Care)
Kanaan, Nicholas (College of Human Medicine. Department of Translational Science and Molecular Medicine)
Fraser, Paul Edward (University of Toronto. Department of Medical Biophysics)
Arancio, Ottavio (Columbia University. Department of Pathology and Cell Biology)
Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular

Fecha:	2016
Resumen:	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.
Ayudas:	Ministerio de Educación PR2010-0297
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	Scientific reports, Vol. 6 (January 2016) , art. 19393, ISSN 2045-2322

DOI: 10.1038/srep19393
PMID: 26786552

15 p, 1.8 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Instituto de Biotecnología y de Biomedicina (IBB)
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