The Role of Oleocanthal in Alzheimer's Disease

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The question asks about the role of oleocanthal in Alzheimer's disease (AD). Oleocanthal, a phenolic compound found in extra-virgin olive oil (EVOO), has been linked to a reduced risk of AD and may offer neuroprotective effects.[1]

The Mediterranean diet, which often includes EVOO, is associated with a lower prevalence of AD and cognitive decline.[2] EVOO contains a significant phenolic fraction, with oleocanthal being one of the most studied compounds.[2] Oleocanthal has demonstrated anti-inflammatory and antioxidant properties.[2]

Several studies suggest that oleocanthal may reduce the risk of AD through multiple mechanisms:

1. Enhancing Amyloid-Beta (Aβ) Clearance: Oleocanthal has been shown to enhance Aβ clearance from the brain.[1] This is achieved by up-regulating P-glycoprotein (P-gp) and LDL lipoprotein receptor-related protein-1 (LRP1) at the blood-brain barrier (BBB), which are major Aβ transport proteins.[1] Studies have demonstrated that oleocanthal treatment increases P-gp and LRP1 expression and activity in brain endothelial cells.[1] In vivo studies using mice have shown that oleocanthal administration enhances Aβ clearance and increases the brain efflux index (BEI%).[1]
2. Aβ Degradation: Oleocanthal treatment has been shown to increase Aβ degradation by up-regulating Aβ degrading enzymes.[1]
3. Anti-inflammatory and Antioxidant Effects: Oleocanthal possesses anti-inflammatory and antioxidant properties.[2]
4. Reducing Aβ Production: EVOO and oleocanthal can reduce the production of Aβ, which further reduces the overall Aβ brain load.[3]
5. Reducing Tau Hyperphosphorylation: EVOO and oleocanthal can reduce tau hyperphosphorylation, another hallmark of AD.[3]

Studies have shown that oleocanthal can interact with Aβ and alter the oligomerization state of Aβ oligomers, protecting neurons from synaptopathological effects associated with Aβ aggregation and plaque formation.[2]

In a study, oleocanthal treatment resulted in a significant increase in the expression of IDE and a small but insignificant increase in NEP in mice brain microvessels.[1] The percent of degraded Aβ peptide (cpm in supernatant) were significantly higher in oleocanthal treated group compared to control.[1]

The findings suggest that oleocanthal, a component of EVOO, may play a role in reducing the risk of AD by enhancing Aβ clearance and degradation, and by reducing neuroinflammation.[1] These findings provide experimental support that potential reduced risk of AD associated with extra-virgin olive oil could be mediated by enhancement of Aβ clearance from the brain.[1]