title: Tau protein is required for amyloid {beta}-induced impairment of hippocampal long-term potentiation.
abstract: Amyloid β (Aβ) and tau protein are both implicated in memory impairment, mild cognitive impairment (MCI), and early Alzheimer's disease (AD), but whether and how they interact is unknown. Consequently, we asked whether tau protein is required for the robust phenomenon of Aβ-induced impairment of hippocampal long-term potentiation (LTP), a widely accepted cellular model of memory. We used wild-type mice and mice with a genetic knock-out of tau protein and recorded field potentials in an acute slice preparation. We demonstrate that the absence of tau protein prevents Aβ-induced impairment of LTP. Moreover, we show that Aβ increases tau phosphorylation and that a specific inhibitor of the tau kinase glycogen synthase kinase 3 blocks the increased tau phosphorylation induced by Aβ and prevents Aβ-induced impairment of LTP in wild-type mice. Together, these findings show that tau protein is required for Aβ to impair synaptic plasticity in the hippocampus and suggest that the Aβ-induced impairment of LTP is mediated by tau phosphorylation. We conclude that preventing the interaction between Aβ and tau could be a promising strategy for treating cognitive impairment in MCI and early AD.
authors.affiliation: Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom.
authors.forename: Olivia A
authors.initials: OA
authors.lastname: Shipton
authors.forename: Julie R
authors.initials: JR
authors.lastname: Leitz
authors.forename: Jenny
authors.initials: J
authors.lastname: Dworzak
authors.forename: Christine E J
authors.initials: CE
authors.lastname: Acton
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Tunbridge
authors.forename: Franziska
authors.initials: F
authors.lastname: Denk
authors.forename: Hana N
authors.initials: HN
authors.lastname: Dawson
authors.forename: Michael P
authors.initials: MP
authors.lastname: Vitek
authors.forename: Richard
authors.initials: R
authors.lastname: Wade-Martins
authors.forename: Ole
authors.initials: O
authors.lastname: Paulsen
authors.forename: Mariana
authors.initials: M
authors.lastname: Vargas-Caballero
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D004594:Electrophysiology; D038362:Glycogen Synthase Kinase 3 / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity; D009474:Neurons / Q000187:drug effects; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D016133:Polymerase Chain Reaction; D016875:tau Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D038362:Glycogen Synthase Kinase 3