Tau protein is required for amyloid {beta}-induced impairment of hippocampal long-term potentiation

TY - JOUR

T1 - Tau protein is required for amyloid {beta}-induced impairment of hippocampal long-term potentiation

AU - Shipton, Olivia A

AU - Leitz, Julie R

AU - Dworzak, Jenny

AU - Acton, Christine E J

AU - Tunbridge, Elizabeth M

AU - Denk, Franziska

AU - Dawson, Hana N

AU - Vitek, Michael P

AU - Wade-Martins, Richard

AU - Paulsen, Ole

AU - Vargas-Caballero, Mariana

PY - 2011/2/2

Y1 - 2011/2/2

N2 - 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.

AB - 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.

KW - Amyloid beta-Peptides

KW - Animals

KW - Blotting, Western

KW - Electrophysiology

KW - Glycogen Synthase Kinase 3

KW - Hippocampus

KW - Long-Term Potentiation

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Neuronal Plasticity

KW - Neurons

KW - Organ Culture Techniques

KW - Peptide Fragments

KW - Phosphorylation

KW - Polymerase Chain Reaction

KW - tau Proteins

U2 - 10.1523/JNEUROSCI.2610-10.2011

DO - 10.1523/JNEUROSCI.2610-10.2011

M3 - Article

C2 - 21289177

SN - 0270-6474

VL - 31

SP - 1688

EP - 1692

JO - Journal of Neuroscience

JF - Journal of Neuroscience

IS - 5

ER -