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Neuroprotective Effects of Extra-Virgin Olive Oil and its Component Oleocanthal in Alzheimer’s disease

Neuroprotective Effects of Extra-Virgin Olive Oil and its Component Oleocanthal in Alzheimer’s disease


Could the addition of EVOO to daily diet prevents, treats, and/or holds AD progression? If yes, why and by what mechanism(s)?


Alzheimer’s disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder of the elderly that afflicts about 30 million patients globally.1 Although the pathogenesis of AD is complex, it involves two well-defined pathologies, amyloid-β (Aβ) and tau-related neuropathologies.2 Amyloid-related neuropathological alterations in the brain are due to accumulation and deposition of Aβ peptides.3 Amyloid peptides, mainly Aβ40 and Aβ42, accumulate in the brain tissue and vasculature of the brain where they assemble and form insoluble plaques, a major hallmark found in the brains of AD patients, as well as soluble oligomers.3,4 The tau-related neuropathological alterations are stimulated by somatodendritic buildup of hyper-phosphorylated tau, which prevents tau assembly onto microtubules and results in intracellular insoluble neurofibrillary tangles (NFTs).6


Extra-virgin olive oil (EVOO)

Diet is a probable risk factor that by modification could reduce or delay the onset of AD. Several epidemiological and clinical studies suggested that adherence to Mediterranean diet improves cognitive function and slows the progression of AD.6-8 Daily consumption of EVOO is one of the characteristic elements of a Mediterranean diet. Dietary consumption of EVOO ranges from 40 to 50 g/day with the highest daily intake among Greeks. The composition of EVOO is primarily monounsaturated fatty acids (~95%) and phenolic compounds (~5%).9,10 Among EVOO phenolics, oleocanthal which is responsible for the bitter and pungent taste of EVOO has shown anti-inflammatory and antioxidant properties similar to the nonsteroidal anti-inflammatory drug ibuprofen.11


EVOO, oleocanthal and AD 

While EVOO beneficial effects were previously reported, the mechanism(s) by which its addition to diet could improve cognitive function was not thoroughly evaluated. Besides, studies focused on studying oleocanthal health benefits against AD were never evaluated in AD models.

Using in vitro and in vivo models complemented with several experimental tools and protocols, studies from my laboratory demonstrated EVOO and oleocanthal are highly efficacious, possess neuroprotective effect against AD and improve cognitive function in AD mouse models.12-16 Further mechanistic studies explained such positive effects as following:

  • EVOO and its bioactive component oleocanthal enhanced the integrity and functionality of the blood-brain barrier (BBB) which is important to maintain healthy brain.
  • EVOO and oleocanthal increased Ab clearance across the BBB.
  • Both EVOO and oleocanthal increased the expression of proteins involved in ApoE-dependent clearance pathway and degradation enzymes of Aβ.
  • EVOO and oleocanthal reduced astrocytes activation and attenuated neuroinflammatory markers that were associated with neuroprotective effect.
  • Besides enhancing its clearance, EVOO reduced the production of Aβ, which further reduced overall Aβ brain load.
  • In addition to reducing Aβ brain load, EVOO reduced tau hyper-phosphorylation, another hallmark of AD.



While clinical studies in humans are necessary to translate our findings, our data support EVOO addition to daily diet protects against AD. The beneficial effect of could be explained, at least in part, by oleocanthal that enhances cognitive function by multiple mechanisms.

View article references

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  2. Selkoe DJ. Alzheimer's disease: genes, proteins, and therapy. Physiol Rev. 2001; 81(2):741-66.
  3. Hardy J. The amyloid hypothesis for Alzheimer's disease: a critical reappraisal. J Neurochem. 2009; 110(4):1129-34.
  4. Lehman EJ, Kulnane LS, Lamb BT. Alterations in beta-amyloid production and deposition in brain regions of two transgenic models. Neurobiol Aging. 2003; 24(5):645-53.
  5. Iqbal K, Liu F, Gong CX, Alonso Adel C, Grundke-Iqbal I. Mechanisms of tau-induced neurodegeneration. Acta Neuropathol. 2009; 118(1):53-69.
  6. Scarmeas N, Stern Y, Tang MX, Mayeux R, Luchsinger JA. Mediterranean diet and risk for Alzheimer's disease. Ann Neurol. 2006;59:912–921.
  7. Gu Y, Nieves JW, Stern Y, Luchsinger JA, Scarmeas N. Food combination and Alzheimer disease risk: a protective diet. Arch Neurol. 2010;67:699–706.
  8. Scarmeas N, Stern Y, Mayeux R, Manly JJ, Schupf N, Luchsinger JA. Mediterranean diet and mild cognitive impairment. Arch Neurol. 2009;66:216–225.
  9. Tripoli E, Giammanco M, Tabacchi G, Di Majo D, Giammanco S, La Guardia M The phenolic compounds of olive oil: structure, biological activity and beneficial effects on human health. Nutr Res Rev. 2005; 18(1):98-112.
  10. Cicerale S, Lucas L, Keast R. Biological activities of phenolic compounds present in virgin olive oil. Int J Mol Sci. 2010; 11(2):458-79.
  11. Beauchamp G. K.; Keast R. S.; Morel D.; Lin J.; Pika J.; Han Q.; Lee C. H.; Smith A. B.; Breslin P. A. (2005) Phytochemistry: ibuprofen-like activity in extra-virgin olive oil. Nature 437, 45–4610.1038/437045a.
  12. Batarseh YS, Mohamed LA, Al Rihani SB, Mousa YM, Siddique AB, El Sayed KA, Kaddoumi A. Oleocanthal ameliorates amyloid-β oligomers toxicity on astrocytes and neuronal cells: In-vitro studies. Neuroscience 2017, 352:204-215.
  13. Qosa H, Batarseh YS, Mohyeldin MM, El Sayed KA, Keller JN, Kaddoumi A. Oleocanthal Enhances Amyloid-β Clearance from the Brains of TgSwDI Mice and in Vitro across a Human Blood-Brain Barrier Model. ACS Chem Neurosci. 2015; 6(11):1849-59.
  14. Qosa H, Mohamed LA, Batarseh YS, Alqahtani S, Ibrahim B, LeVine H 3rd, Keller JN, Kaddoumi A. Extra-virgin olive oil attenuates amyloid-β and tau pathologies in the brains of TgSwDI mice. J Nutr Biochem. 2015; S0955-2863(15)00189-8.
  15. Abuznait AH, Qosa H, Busnena B, El Sayed KA, Kaddoumi A. Olive Oil-Derived Oleocanthal Enhances β-Amyloid Clearance as a Potential Neuroprotective Mechanism against Alzheimer’s Disease: In-vitro and In-vivo Studies. ACS Chem Neurosci. 2013; 4(6):973-82.
  16. Abuznait A, Qosa H, Mohamed LA, Batarshe YS, Kaddoumi A. “Neuroprotective effects of olive oil components in Alzheimer disease” in Neuroprotective Effects of Phytochemicals in Neurological disorders. Editors:  Farooqui T, Farooqui AA. Wiley Blackwell. 2017. 299 p.