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

Abstract

ObjectiveConsumption 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.MethodsHerein, 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.ResultsTriple 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 Aβ peptide levels and deposition, lower amount of phosphorylated tau protein at specific epitopes, which were secondary to an activation of cell autophagy.InterpretationTaken together, our findings support a beneficial effect of EVOO consumption on all major features of the AD phenotype (behavioral deficits, synaptic pathology, Aβ and tau neuropathology), and demonstrate that autophagy activation is the mechanism underlying these biological actions.

Oleocanthal-Rich Extra-Virgin Olive Oil Restores the Blood–Brain Barrier Function through NLRP3 Inflammasome Inhibition Simultaneously with Autophagy Induction in TgSwDI Mice

“…In this study, the 3-months consumption of EVOO significantly increased several autophagy markers that regulate autophagy induction and maturation in the brains of TgSwDI mice. Our findings confirm an earlier observation for EVOO effect on inducing autophagy where its chronic administration significantly increased levels of the autophagy activation biomarkers ATG5 and ATG7 in the brains of 3xTg mice . In an effort to expand on the mechanism by which EVOO induced autophagy, AMPK and mTOR pathways were evaluated.…”

Extra-Virgin Olive Oil Enhances the Blood–Brain Barrier Function in Mild Cognitive Impairment: A Randomized Controlled Trial

“…While further studies are necessary to confirm these results, reduced Aβ ratios could be explained by reduced production and increased peripheral clearance of Aβ. Similarly, ROO and EVOO significantly reduced the p-tau/t-tau ratio, an effect that could be influenced by the mild reduction in blood p-tau 181 (ROO, not significant; EVOO, p = 0.05), which is consistent with our preclinical observations in TgSwDI and 3xTg mouse models where EVOO reduced tau neuropathology [ 18 , 19 , 20 ]. The results also suggest reduced p-tau/t-tau ratio could be affected by the reduced Aβ levels and thus reduced tau phosphorylation [ 49 , 50 , 51 ].…”

Dietary Anti-Aging Polyphenols and Potential Mechanisms

“…Dietary intake of 10% olive oil (contains 532 mg gallic acid/kg oil) for 4.5 months significantly reduced oxidative stress in the senescence-accelerated mouse prone 8 (SAMP8) mice, which was mediated by the induction of nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent gene expressions [ 39 ]. These results are in line with a new report that dietary intake of extra virgin olive oil for 6 months significantly ameliorated cognition decline in a transgenic mouse model with brain amyloid plaques and neurofibrillary tangles [ 40 ]. In a study with diabetic rats, it was also shown that a 3-month treatment with virgin olive oil (0.125 mg/kg phenols per day) displayed a stronger neuroprotective ability than that of aspirin (2 mg/kg per day) [ 41 ].…”