title: Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory.
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.
authors.affiliation: Department of Pathology and Cell Biology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, 630 W 168th St. New York, NY 10032 USA.
authors.forename: M
authors.initials: M
authors.lastname: Fá
authors.affiliation: Department of Pathology and Cell Biology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, 630 W 168th St. New York, NY 10032 USA.|Department of Biomedical and Biotechnological Sciences, Section of Physiology, University of Catania, Catania, 95125 Italy.
authors.forename: D
authors.initials: D
authors.lastname: Puzzo
authors.affiliation: Institute of Human Physiology, Università Cattolica del Sacro Cuore, Rome, 00168 Italy.
authors.forename: R
authors.initials: R
authors.lastname: Piacentini
authors.affiliation: Department of Pathology and Cell Biology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, 630 W 168th St. New York, NY 10032 USA.
authors.forename: A
authors.initials: A
authors.lastname: Staniszewski
authors.affiliation: Department of Pathology and Cell Biology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, 630 W 168th St. New York, NY 10032 USA.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Cell Biology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, 630 W 168th St. New York, NY 10032 USA.|Department of Biochemistry and Molecular Biology, Institute of Biotechnology and Biomedicine, Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Baltrons
authors.affiliation: Institute of Human Physiology, Università Cattolica del Sacro Cuore, Rome, 00168 Italy.
authors.forename: D D
authors.initials: DD
authors.lastname: Li Puma
authors.affiliation: Department of Pathology and Cell Biology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, 630 W 168th St. New York, NY 10032 USA.|Oligomerix, Inc., Oligomerix, Inc., 7 Legion Drive, Suite 101, Valhalla, NY 10595, USA.
authors.forename: I
authors.initials: I
authors.lastname: Chatterjee
authors.affiliation: Department of Pathology and Cell Biology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, 630 W 168th St. New York, NY 10032 USA.|Department of Neurology, Third Military Medical University, Chongqing, 400042, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pathology and Cell Biology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, 630 W 168th St. New York, NY 10032 USA.
authors.forename: F
authors.initials: F
authors.lastname: Saeed
authors.affiliation: Department of Pathology and Cell Biology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, 630 W 168th St. New York, NY 10032 USA.
authors.forename: H L
authors.initials: HL
authors.lastname: Berman
authors.affiliation: Institute of Human Physiology, Università Cattolica del Sacro Cuore, Rome, 00168 Italy.
authors.forename: C
authors.initials: C
authors.lastname: Ripoli
authors.affiliation: Department of Biomedical and Biotechnological Sciences, Section of Physiology, University of Catania, Catania, 95125 Italy.
authors.forename: W
authors.initials: W
authors.lastname: Gulisano
authors.affiliation: Translational Technology Core Laboratory, Rockefeller University, New York, NY 10065, USA.
authors.forename: J
authors.initials: J
authors.lastname: Gonzalez
authors.affiliation: Department of Chemical Engineering, ASU, Tempe, AZ 85281, USA.
authors.forename: H
authors.initials: H
authors.lastname: Tian
authors.affiliation: Department of Pathology and Cell Biology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, 630 W 168th St. New York, NY 10032 USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Costa
authors.affiliation: Oligomerix, Inc., Oligomerix, Inc., 7 Legion Drive, Suite 101, Valhalla, NY 10595, USA.
authors.forename: P
authors.initials: P
authors.lastname: Lopez
authors.affiliation: Oligomerix, Inc., Oligomerix, Inc., 7 Legion Drive, Suite 101, Valhalla, NY 10595, USA.
authors.forename: E
authors.initials: E
authors.lastname: Davidowitz
authors.affiliation: Department of Pathology and Cell Biology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, 630 W 168th St. New York, NY 10032 USA.
authors.forename: W H
authors.initials: WH
authors.lastname: Yu
authors.affiliation: Department of Psychiatry, The Mount Sinai School of Medicine, JJ-Peters VA Medical Center, Bronx, NY 10468, USA.
authors.forename: V
authors.initials: V
authors.lastname: Haroutunian
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Brown
authors.affiliation: Department of Biomedical and Biotechnological Sciences, Section of Physiology, University of Catania, Catania, 95125 Italy.
authors.forename: A
authors.initials: A
authors.lastname: Palmeri
authors.affiliation: Department of Neuroscience and Physiology, NYU Langone Medical Center, New York, NY 10016, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Sigurdsson
authors.affiliation: Department of Pathology and Cell Biology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, 630 W 168th St. New York, NY 10032 USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Duff
authors.affiliation: Department of Pathology and Cell Biology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, 630 W 168th St. New York, NY 10032 USA.
authors.forename: A F
authors.initials: AF
authors.lastname: Teich
authors.affiliation: Department of Pathology and Cell Biology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, 630 W 168th St. New York, NY 10032 USA.
authors.forename: L S
authors.initials: LS
authors.lastname: Honig
authors.affiliation: Translational Technology Core Laboratory, Rockefeller University, New York, NY 10065, USA.
authors.forename: M
authors.initials: M
authors.lastname: Sierks
authors.affiliation: Oligomerix, Inc., Oligomerix, Inc., 7 Legion Drive, Suite 101, Valhalla, NY 10595, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: Moe
authors.affiliation: Department of Microbiology and Immunology, Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: L
authors.initials: L
authors.lastname: D'Adamio
authors.affiliation: Institute of Human Physiology, Università Cattolica del Sacro Cuore, Rome, 00168 Italy.|San Raffaele Pisana Scientific Institute for Research, Hospitalization and Health Care, Rome, 00163, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Grassi
authors.affiliation: Department of Translational Science and Molecular Medicine, College of Human Medicine, MSU, Grand Rapids, MI, 49503, USA.
authors.forename: N M
authors.initials: NM
authors.lastname: Kanaan
authors.affiliation: Tanz Centre for Research in Neurodegenerative Diseases and Department of Medical Biophysics, University of Toronto, 60 Leonard Avenue, Toronto, Ontario M5T 2S8 Toronto, Canada.
authors.forename: P E
authors.initials: PE
authors.lastname: Fraser
authors.affiliation: Department of Pathology and Cell Biology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, 630 W 168th St. New York, NY 10032 USA.
authors.forename: O
authors.initials: O
authors.lastname: Arancio
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D005110:Extracellular Space / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D017774:Long-Term Potentiation; D008568:Memory; D051379:Mice; D009474:Neurons / Q000378:metabolism; D066329:Protein Aggregates; D066263:Protein Aggregation, Pathological; D055503:Protein Multimerization; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D066329:Protein Aggregates; D016875:tau Proteins