Synaptic Released Zinc Promotes Tau Hyperphosphorylation by Inhibition of Protein Phosphatase 2A (PP2A)

Background: Tangle distribution is largely overlapped with zinc-containing glutamatergic neurons. Synaptically released zinc may be involved in tau hyperphosphorylation. Results: Increased synaptic activity induces tau hyperphosphorylation by synaptic zinc through PP2A inhibition. Conclusion: Synaptic activity promotes tau hyperphosphorylation, and synaptically released zinc plays a central role. Significance: Therapies targeted to maintaining zinc homeostasis and moderating synaptic activity may benefit AD by reducing tauopathy.