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.

Characterization of Olive Oil Phenolic Extracts and Their Effects on the Aggregation of the Alzheimer’s Amyloid-β Peptide and Tau

“…The Mediterranean diet has been widely promoted as being protective against several pathological diseases, including AD, − which affects 44 million people worldwide and has a predicted economic burden of $600 billion in the US alone by 2050 . Several preclinical and epidemiological studies have linked the consumption of EVOO in particular to the amelioration of AD symptoms . Positive effects of an EVOO-enriched diet were demonstrated in a triple transgenic (3xTg) AD mouse model expressing both Aβ and tau pathologies, including enhanced behavioral performance, reduced insoluble Aβ deposition, and decreased tau phosphorylation .…”

“… 76 Several preclinical and epidemiological studies have linked the consumption of EVOO in particular to the amelioration of AD symptoms. 77 Positive effects of an EVOO-enriched diet were demonstrated in a triple transgenic (3xTg) AD mouse model expressing both Aβ and tau pathologies, including enhanced behavioral performance, reduced insoluble Aβ deposition, and decreased tau phosphorylation. 78 Clinical studies of EVOO intervention in patients with mild cognitive impairment (MCI), an early indicator of AD, have shown potential benefits.…”

Oxidative Stress as a Target for Non-Pharmacological Intervention in MAFLD: Could There Be a Role for EVOO?

“…Several studies have focused on EVOO and its compounds, showing beneficial effects on body weight (quantitative reduction) [ 112 ], adipose tissue (quantitative reduction and positive metabolic modulation) [ 113 , 114 ], lipidic ratio (reduction of total cholesterol (TC), TC/high-density lipoproteins (HDL), and low-density lipoprotein (LDL) oxidation; increase of HDL concentrations) [ 115 , 116 ], glycemic metabolism (reduction of T2DM incidence, fasting glucose, and advanced glycosylated end-products, including glycated hemoglobin; activation of the glucagon-like peptide-1 (GLP-1) incretin-pattern) [ 117 , 118 , 119 , 120 ], and cardiovascular risk (reduction of LDL oxidation, systolic blood pressure, and cardiovascular events, improvement of nitric oxide (NO)-mediated endothelial function) [ 121 , 122 , 123 , 124 ]. To a further extent, but with a lesser degree of evidence (mostly preclinical studies), EVOO intake showed effectiveness in the reduction/modulation of autoimmune [ 125 , 126 , 127 , 128 , 129 ], inflammatory bowel [ 130 , 131 , 132 , 133 ], neurodegenerative [ 134 , 135 , 136 , 137 , 138 ], and neoplastic diseases [ 137 , 139 , 140 ], as well as gut microbiota alterations [ 141 , 142 , 143 , 144 ].…”