Background: Ginkgo biloba extract EGb761 has shown the neuroprotective effects on Alzheimer's
disease (AD) through the protection against the Aβ-induced neurotoxicity. However, it is not
completedly clear whether EGb761 attenuates tau hyperphosphorylation, another of the most prominent
mechanisms underlying the pathology of AD.
Methods: we employed hyperhomocysteinemia (HHcy) to mimic AD like pathological alterations and
memory deficits in rats as model, and injected EGb761 with or after HHcy injection as prevention and
treatment, injected saline as control. We measured the status of oxidative damage and spatial and learning
memory in rats. Then we detected the level of memory-related proteins, tau phosphorylation and the
level and activity of tau kinase (GSK-3β) and phosphatase (PP2A) by Western blotting and Immunohistochemistry.
Results: We found that EGb761 could significantly antagonize HHcy-induced oxidative damage, recover
PP2Ac and GSK3β activities deregulated by HHcy. Furthermore, tau was hyperphosphorylated at
Thr231, Ser262, Ser396, and Ser404, most common PP2Ac and GSK3β targeted sites in the hippocampus
and prefrontal cortex of HHcy rats, whereas EGb761 recovered the tau phosphorylation at those
sites. Behavioral tests revealed that EGb761 rescued HHcy-induced spatial reference memory deficit
and upregulated the expression of synapse-associated protein PSD95 and synapsin-1.
Conclusion: EGb761 might be a promising drug to treat AD through its anti-oxidative activity and decreasing
tau hyperphosphorylation besides the protection against the Aβ-induced neurotoxicity.