Extra-Virgin Olive Oil and Oleocanthal Reduce Amyloid ß Load in Alzheimer's Disease Mouse Model

Mediterranean diet (MD) is considered one of the most health promoting diets adopted initially by the Mediterranean population. Recent studies showed a link between MD and lowering the incidence of mild cognitive impairment and Alzheimer's disease (AD). Clinical and preclinical studies have suggested several health promoting effects for the dietary consumption of extra-virgin olive oil (EVOO), a major component of MD, that could protect and decrease the risk of developing AD. Moreover, recent studies have linked this protective effect to oleocanthal, a phenolic secoiridoid component of EVOO. Here we provide evidence to support the role of EVOO and oleocanthal in enhancing the clearance of amyloid-beta (Aß), a major pathological hallmark in AD, and reducing the overall inflammatory burden on the brain. In our study, both EVOO and oleocanthal treatment significantly decreased Aß load in the hippocampal parenchyma and microvessels. Furthermore, our mechanistic studies demonstrated an effect on increasing the expression of important amyloid clearance proteins at the blood-brain barrier (BBB) including P-glycoprotein (P-gp) and low density lipoprotein receptor-related protein 1 (LRP1), and to activate the ApoE-dependent amyloid clearance pathway in the mice brains. Additionally, oleocanthal was able to reduce astrocytes activation and IL-1ß levels. The reduction in Aß levels and microvessels deposition could be explained, at least in part, to the enhanced Aß clearance across the BBB and by ApoE-dependent pathway. In addition, oleocanthal demonstrated an anti-inflammatory effect by reducing astrocytes activation and IL-1ß brain levels, which emphasize the importance of considering EVOO and oleocanthal as a potential therapeutic interventions in AD.