Abstract
In recent years, increasing evidence has accumulated supporting the health benefits of extra virgin olive oil (EVOO). Previous studies showed that EVOO supplementation improves Alzheimer's disease (AD)-like amyloidotic phenotype of transgenic mice. However, while much attention has been focused on EVOO-mediated modulation of Aβ processing, its direct influence on tau metabolism in vivo and synaptic function is still poorly characterized. In this study, we investigated the effect of chronic supplementation of EVOO on the phenotype of a relevant mouse model of tauopathy, human transgenic tau mice (hTau). Starting at 6 months of age, hTau mice were fed chow diet supplemented with EVOO or vehicle for additional 6 months, and then the effect on their phenotype was assessed. At the end of the treatment, compared with control mice receiving EVOO displayed improved memory and cognition which was associated with increased basal synaptic activity and short-term plasticity. This effect was accompanied by an upregulation of complexin 1, a key presynaptic protein. Moreover, EVOO treatment resulted in a significant reduction of tau oligomers and phosphorylated tau at specific epitopes. Our findings demonstrate that EVOO directly improves synaptic activity, short-term plasticity, and memory while decreasing tau neuropathology in the hTau mice. These results strengthen the healthy benefits of EVOO and further support the therapeutic potential of this natural product not only for AD but also for primary tauopathies.