Extra-virgin olive oil ameliorates cognition and neuropathology of the 3xTg mice: role of autophagy.

Objective: Consumption of extra virgin olive oil (EVOO), a major component of the Mediterranean diet, has been associated with reduced incidence of Alzheimer's disease (AD). However, the mechanisms involved in this protective action remain to be fully elucidated.

Methods: Herein, we investigated the effect of daily consumption of EVOO on the AD-like phenotype of a mouse mode of the disease with plaques and tangles.

Results: Triple transgenic mice (3xTg) received either regular chow or a chow diet supplemented with EVOO starting at 6 months of age for 6 months, then assessed for the effect of the diet on the AD-like neuropathology and behavioral changes. Compared with controls, mice receiving the EVOO-rich diet had an amelioration of their behavioral deficits, and a significant increase in the steady state levels of synaptophysin, a protein marker of synaptic integrity. In addition, they had a significant reduction in insoluble A peptide levels and deposition, lower amount of phosphorylated tau protein at specific epitopes, which were secondary to an activation of cell autophagy.

Interpretation: Taken together, our findings support a beneficial effect of EVOO consumption on all major features of the AD phenotype (behavioral deficits, synaptic pathology, A and tau neuropathology), and demonstrate that autophagy activation is the mechanism underlying these biological actions.