Extra-Virgin Olive Oil in Alzheimer's Disease: A Comprehensive Review of Cellular, Animal, and Clinical Studies

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is characterized by several pathological hallmarks, including the deposition of amyloid-β (Aβ) plaques, neurofibrillary tangles, blood-brain barrier (BBB) dysfunction, increased oxidative stress, and neuroinflammation. Current treatment options include monoclonal antibody drugs, acetylcholinesterase, and n-methyl-d-aspartate (NMDA) antagonists. Although those treatments provide some improvements in patients' quality of life, they fail to prevent or cure AD. Current research aims to identify novel targets and tools for AD prevention and modification. In this context, several studies showed the beneficial effect of the Mediterranean diet in the prevention and treatment of AD. One integral component of the Mediterranean diet is olive oil and extra-virgin olive oil (EVOO), which is high in phenolic compounds. EVOO and other olive-related phenolic compounds have been shown to reduce the risk of developing mild cognitive impairment (MCI) and AD. In this review, we discuss the mechanisms by which EVOO and phenolic compounds exert neuroprotective effects, including modulation of AD pathologies and promotion of cognitive health. Findings indicate that EVOO and its phenolic constituents influence key pathological processes of AD, such as Aβ aggregation, tau phosphorylation, and neuroinflammation, while also enhancing BBB integrity and reducing oxidative stress. The human studies cited reveal a consistent trend where the consumption of olive oil is associated with cognitive benefits and a decreased risk of AD and related dementias. In conclusion, EVOO and its phenolic compounds hold promising potential for the prevention and treatment of AD, representing a significant shift towards more effective strategies against this complex neurodegenerative disorder.

Keywords: Alzheimer’s disease (AD); EVOO; EVOO phenolic compounds; amyloid-β; autophagy; blood–brain barrier; extra-virgin olive oil; neuroinflammation; olive oil; oxidative stress; tau.

Figure 1

The chemical structures of selected phenolic compounds in EVOO.

Figure 2

Fundamental pathological features and molecular mechanisms implicated in the progression of AD, revealing critical targets for therapeutic ligand intervention. Abbreviations: nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), phosphoinositide 3-kinases/protein kinase B (PI3K/Akt), AMP-activated protein kinase (AMPK), cyclooxygenase (COX), zonula occludens-1 (ZO-1), vascular endothelial cadherin (VE-Cadherin), matrix metalloproteinases (MMPs), amyloid beta (Aβ), amyloid precursor protein (APP), apolipoprotein E (APOE), beta-site APP cleaving enzyme 1 (BACE1), glycogen synthase kinase-3 beta (GSK-3β), nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE), mitogen-activated protein kinases (MAPK), reactive oxygen species (ROS), AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), phosphoinositide 3-kinases/protein kinase B (PI3K/Akt), PTEN-induced kinase 1/Parkin (PINK1/Parkin), vacuolar protein sorting 34 (Vps34).

Figure 3

Neuropathological key features of AD (left) contrasted with the neuroprotective effects of EVOO and phenolic compounds (right).