Entry #: 47
Date: 28 April 2018
Section: Neurodegeneration
Topic: Extra-virgin olive oil and Alzheimer’s disease
Type: In vivo model

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Expert review of literature related to olives and olive oil

D. Elizabeth McCord, Nancy B. Ray and Tom C. Karagiannis

Title

Oleocanthal-rich extra-virgin olive oil enhances donepezil effect by reducing amyloid-Β load and related toxicity in a mouse model of Alzheimer’s disease

Author(s)

Batarseh Y and Kaddoumi A

Citation / Year

(1) / 2018

Keywords

Extra-virgin olive oil, oleocanthal, Alzheimer’s disease, amyloid-Β, neurodegeneration, donepezil

Summary

Alzheimer’s disease is the most common chronic progressive neurodegenerative disease (2). The hallmark of Alzheimer’ disease is the accumulation of extracellular amyloid-Β plaques which is the result of processing of the amyloid precursor protein by secretase enzymes (3). The insoluble AΒ peptide forms aggregates known as oligomers, which then progress to plaques; this pathogenic form of the AΒ peptide and resulting aggregates form the underlying pathology of Alzheimer’s disease (4). Currently, pharmacological interventions for the disease are limited, with available treatments only attenuating symptoms. For example, the acetylcholinesterase inhibitor, donepezil, provides some symptomatic benefits but not a curative effect, although there is evidence that compound has effects on AΒ pathology, and has been shown to enhance AΒ clearance via the blood-brain-barrier (5-7). In this study, the authors aimed to investigate the effects of a medical food in augmenting the effects of donepezil in a mouse model of Alzheimer’s disease. The rationale for the choice of the medical food, in this case oleocanthal-rich extra-virgin olive oil, was based on the emerging evidence highlighting the beneficial effects of the Mediterranean diet in the progression of Alzheimer’s disease (8-10).

Key points and implications

The 5xFAD mouse model was utilised in this study and mice were divided into four groups (n=12 per group with six male and six female mice per group): 1) control group, 2) extra-virgin olive oil group for three months (from one month to four months), 3) donepezil group in which mice were treated with 1 mg per kg per day of donepezil for one month starting at the age of four months, and 4) the extra-virgin olive oil and donepezil group in which the interventions were administered as described in 2) and 3). The olive oil chosen for this study was “The Governor” originated from Corfu, Greece, and selection was based on the high quantity of oleocanthal (680 mg per kg). for the study, the extra-virgin olive oil diet was prepared (mixture of extra-virgin olive oil with powdered diet), to produce a dose of 0.7 g per kg per day to provide equivalence with levels of extra-virgin olive oil consumed as part of the Mediterranean diet (50 g per day); providing a total dose of 476 μg per kg per day of oleocanthal which was replenished every other day. Following administration of the dietary intervention and donepezil as series of experiments were performed to investigate the effects of extra-virgin olive oil on the effects of donepezil. The key experiments and findings were as follows: 1) hippocampal histological analysis indicated significant reduction of AΒ-load in the hippocampus following treatment with extra-virgin olive oil and donepezil, 2) total amyloid content was not altered but processing of the protein was modulated by extra-virgin olive oil and donepezil with increases in Β- and decreases in Β-metabolism, 3) an increase in the expression of the member 1 of human transporter sub-family ABCA (ABCA1) and peroxisome proliferator-activated receptor gamma (PPAR-γ) were observed with extra-virgin olive oil and donepezil, 4) extra-virgin olive oil and donepezil modulated the expression of proteins associated with AΒ clearance and blood-brain-barrier tightness, 5) unlike donepezil, which only exhibited mild effects on inflammation, extra-virgin olive oil reduced neuroinflammation and enhanced antioxidant capacity, as measured by IL-1Β levels, astrocyte activation, and antioxidant levels, and 6) extra-virgin olive oil did not interfere with the increased acetylcholine levels (cholinergic mechanism), induced by donepezil. Overall, these findings highlight the favourable combination of extra-virgin olive oil with donepezil in a model of Alzheimer’s disease, importantly the findings indicate that 1) extra-virgin olive oil may influence numerous molecular pathways associated with disease, 2) combinations of extra-virgin olive oil with acetylcholinesterase inhibitors may have beneficial effects in disease with some overlapping and various complimentary effects, and 3) extra-virgin olive oil does not interfere with the central mechanism of acetylcholinesterase inhibitors. These exciting findings provide a framework for further research in the field.

Related publications

  1. Y. S. Batarseh, A. Kaddoumi, Oleocanthal-rich extra-virgin olive oil enhances donepezil effect by reducing amyloid-beta load and related toxicity in a mouse model of Alzheimer’s disease. The Journal of nutritional biochemistry 55, 113-123 (2017).
  2. M. Citron, Alzheimer’s disease: strategies for disease modification. Nature reviews. Drug discovery 9, 387-398 (2010).
  3. D. J. Selkoe, Alzheimer’s disease: genes, proteins, and therapy. Physiological reviews 81, 741-766 (2001).
  4. J. Hardy, The amyloid hypothesis for Alzheimer’s disease: a critical reappraisal. Journal of neurochemistry 110, 1129-1134 (2009).
  5. D. A. Casey, D. Antimisiaris, J. O’Brien, Drugs for Alzheimer’s disease: are they effective? P & T : a peer-reviewed journal for formulary management 35, 208-211 (2010).
  6. H. G. Kim et al., Donepezil inhibits the amyloid-beta oligomer-induced microglial activation in vitro and in vivo. Neurotoxicology 40, 23-32 (2014).
  7. L. A. Mohamed, H. Qosa, A. Kaddoumi, Age-Related Decline in Brain and Hepatic Clearance of Amyloid-Beta is Rectified by the Cholinesterase Inhibitors Donepezil and Rivastigmine in Rats. ACS chemical neuroscience 6, 725-736 (2015).
  8. N. Scarmeas, Y. Stern, M. X. Tang, R. Mayeux, J. A. Luchsinger, Mediterranean diet and risk for Alzheimer’s disease. Annals of neurology 59, 912-921 (2006).
  9. K. L. Tuck, P. J. Hayball, Major phenolic compounds in olive oil: metabolism and health effects. The Journal of nutritional biochemistry 13, 636-644 (2002). Entry #: 47 Date: 28 April 2018 Section: Neurodegeneration Topic: Extra-virgin olive oil and Alzheimer’s disease Type: In vivo model
  10. Page 3 of 3 Copyright © 2017 McCord Research, Inc. Archived at: www.mccordresearch.com.au
  11. S. Cicerale, L. Lucas, R. Keast, Biological activities of phenolic compounds present in virgin olive oil. International journal of molecular sciences 11, 458-479 (2010).