Tau Protein Is Required for Amyloid β-Induced Impairment of Hippocampal Long-Term Potentiation

Amyloid beta (A beta) 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 A beta-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 A beta-induced impairment of LTP. Moreover, we show that A beta increases tau phosphorylation and that a specific inhibitor of the tau kinase glycogen synthase kinase 3 blocks the increased tau phosphorylation induced by A beta and prevents A beta-induced impairment of LTP in wild-type mice. Together, these findings show that tau protein is required for A beta to impair synaptic plasticity in the hippocampus and suggest that the A beta-induced impairment of LTP is mediated by tau phosphorylation. We conclude that preventing the interaction between A beta and tau could be a promising strategy for treating cognitive impairment in MCI and early AD.