Consuming Extra Virgin Olive Oil could be a Viable Therapeutic Opportunity for Preventing or Halting Dementia and Alzheimer’s Disease

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Researchers from the Lewis Katz School of Medicine at Temple University (LKSOM) published a study online on June 21, 2017 in the Annals of Clinical and Translational Neurology which identifies extra virgin olive oil (EVOO) as protective against cognitive decline.  1

The consumption of EVOO shows great promise against the classic markers of dementia and Alzheimer’ disease.  What this new study demonstrated where the following discoveries from EVOO:

  • Reduces neuro-inflammation
  • Activates autophagy
  • Restores and protects working and spatial memory and learning ability 
  • Reduces the formation of amyloid-beta plaques
  • Reduces the formation of neurofibrillary tangles from phosphorylated tau
  • Does not effect CREB signaling

In this study, the researchers used a well-established Alzheimer’s disease mouse model known as triple transgenic mice (3xTg).

Triple transgenic mice (3xTg) contain three mutations associated with familial Alzheimer’s disease:

  • APP Swedish
  • MAPT P301L
  • PSEN1 M146V

Image result for Triple transgenic mice

Figure 1. Triple transgenic mouse model.   (Source)

Due to these mutations, these mice develop the three characteristics of Alzheimer’s disease, namely:

  • amyloid plagues
  • memory impairment
  • neurofibrillary tangles

The mice are viable, fertile, and display no initial gross physical or behavioral abnormalities. These mice display both plaque and tangle pathology.

Amyloid beta deposition is progressive, with intracellular immunoreactivity detected in some brain regions as early as three to four months of age. Extracellular Amyloid beta deposits appear by six months in the frontal cortex and become more extensive by twelve months.

Changes in tau occur later; by 12 to 15 months aggregates of conformationally-altered and hyper-phosphorylated tau are detected in the hippocampus.  2  

The researchers feed two groups of triple transgenic mice, a group that received a chow diet with EVOO starting at 6 months of age for a period of 6 months, and the other group as a control group that received no EVOO enhanced chow.  At 6 months of age is when there are no symptoms of Alzheimer’s disease in the triple transgenic mice.

At 9 months of age, the researchers started to assess the effect of the diet on Alzheimer’s disease neuropathology and behavioral changes.

At 9 and 12 months of age, the researchers observed that the group on the EVOO enriched chow diet improved cognitive function and and found that the Alzheimer’s markers were improved.

Specifically, the researchers found six discoveries from their experiment on the triple transgenic mice fed the EVOO enriched diet:

EVOO-rich diet restores working and spatial memory in 3xTg mice

The mice were tested at age of 9 and 12 months in the Y-maze.  The mice at 9 and 12 months showed a reduction in the number of entries that reached the statistical significance for the control (non-EVOO diet) group at 9 months.  When the researchers assessed the percentage of alternation, they observed a reduction of this parameter in the control group at both 9 and 12 months but, this was completely rescued in the EVOO treated mice.

EVOO-rich diet reduces Amyloid beta levels and deposition in 3xTg mice

At 12 months of age, mice were euthanized and brain cortex homogenates was assayed for amyloid beta levels in the RIPA-soluble and formic acid-soluble fractions. Compared with controls, we found that EVOO group presented a decrease in amyloid beta1-40 levels that reached the statistical significance.

EVOO-rich diet attenuates tau pathology

Phosphorylated tau is responsible for neurofibrillary tangles, which are suspected of contributing to the nerve cell dysfunction in the brain that is responsible for Alzheimer’s memory symptoms.

The researchers found a significant reduction in the phosphorylated forms of tau at Ser202/Thr205 and Ser396/Ser404, as recognized by the antibodies AT8 and PHF13, respectively, in the EVOO group when compared with mice on a regular diet (control group).

EVOO-rich diet improves synapse integrity and neuro-inflammation

To assess whether the improved cognitive performance and Alzheimer’s disease pathology seen in the EVOO-treated mice was also biochemically characterized by an amelioration of synaptic integrity, we assayed the steady state levels of two major synaptic proteins: synaptophysin (SYP) indices of presynaptic integrity, and the postsynaptic density protein 95 (PSD95).

No differences were observed between the two groups when PSD95 levels were measured. By contrast, mice fed with EVOO-rich diet when compared with the control group, displayed a statistically significant increase in the steady state levels of SYP.

EVOO-rich diet does not affect CREB signaling on 3xTg mice

CREB (cAMP response element-binding protein) is a cellular transcription factor which binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the downstream genes.

CREB has a well-documented role in neuronal plasticity and long-term memory formation in the brain and has been shown to be integral in the formation of spatial memory.  CREB downregulation is implicated in the pathology of Alzheimer’s disease and increasing the expression of CREB is being considered as a possible therapeutic target for Alzheimer’s disease.

The researchers investigated the effect of our EVOO-rich diet on total CREB levels and its phosphorylated form at Ser133 (p-CREB). The levels of total CREB and p-CREB were not changed in the brain of EVOO-treated mice compared to controls. Additionally, no differences were detected in the protein expression level of BDNF and cFos, two important CREB target genes, between the two groups

EVOO-rich diet induces autophagy in 3xTg mice

Autophagy is the process by which cells break down and clear out intracellular debris and toxins, such as amyloid plaques and tau tangles.  It is often thought that a reduction in autophagy marks the beginning of Alzheimer’s disease.

Finally, the researchers looked at several autophagy markers, including ATG5-12, ATG7 and the microtubule-associated protein light chain 3 conversion (LC3I/II) which are considered essential for the autophagosome formation and autophagic flux, respectively.  In this study, ATG5 and ATG7 immunoreactivity was significantly stronger in EVOO-treated mice compared to controls suggesting induction of autophagy in this group of 3xTg mice.

The researchers had a very favorable conclusion as it related to the consumption of EVOO and its prevention of dementia and Alzheimer’s disease.  They stated:

“In conclusion, our investigation establishes for the first time to the best of our knowledge a protective effect of EVOO in modulating tau phosphorylation, memory impairments, synaptic integrity, and neuro-inflammation in a mouse model of AD with plaques and tangles.

The translational value of our findings lies in the observation that EVOO supplementation can influence the entire spectrum of the AD phenotype. Our studies provide mechanistic support to the positive cross-sectional and longitudinal data on this component of the Mediterranean diet, and most importantly the biological rationale to the novel hypothesis that EVOO could be considered as a viable therapeutic opportunity for preventing or halting AD.”  3

Extra Virgin Olive Oil

It is important to note that the olive oil used in this study was a high phenolic content EVOO. High phenolic EVOO contains a higher number of polyphenols and a higher percentage of those polyphenols than regular EVOO. 

EVOO contains many polyphenols, at least up to thirty.  The more important polyphenols in EVOO include:

  • 10-hydroxyligstroside
  • 10-hydroxyoleuropein
  • elenolic acid
  • flavonoids
  • hydroxytyrosol
  • lignans
  • ligstroside
  • oleuropein
  • pinoresinol
  • tyrosol
  • olecanthal
  • oleacein
  • oleuropein aglycon

The grade of olive oil will determine the amount of polyphenols contained in the oil.  Ordinary grades of olive oil contain 50 ppm or less of polyphenols, depending on their percentage of refined olive oil.

With Extra Virgin Olive Oil, the polyphenol content typically ranges between 100 to 250 ppm.

Exceptional grades of Extra Virgin Olive Oil may be as high as 500 ppm or higher.  This higher content of polyphenols will depend on a number of factors such as:

  • age of the oil
  • degree of ripeness
  • olive cultivar
  • production and extraction technologies employed

Extra virgin olive oil generally falls into three categories:

  • delicate
  • medium
  • robust

The robust olive oils tend to have the highest levels of polyphenols. This can be indicated by the olive oil having a strong peppery finish, a distinct bitterness and very intense flavors on the front end of the palate.

A superior and exceptional EVOO with a very high phenolic content is The Governor™, which is grown and produced on the island of Corfu, Greece.

Figure 2.  The Governor™ Premium variety  (Copyright The Governor™)

The Governor™ has two varieties:

  • The Governor™ Premium
  • The Governor™ Limited

The Governor™ was scientifically tested in March 2014 at the University of Athens and compared with the results of 700 other olive oil samples, from 30 different olive varieties. 150 of the comparative olive oil samples originated from countries outside Greece, specifically: California, Italy, Spain, Croatia, Tunisia, Cyprus, France, Argentina, Chile, Morocco and Israel.

The results were impressive. The oleocanthal and oleacein concentrations in The Governor™ are 7 times higher than the average of the samples and the highest value recorded among all commercially-available bottled oils since 2009.

Oleocanthal, oleocein and other elements present in The Governor™ olive oil present important biological activity, and are related with anti-inflammatory, antioxidant and neuro-protective benefits.

The total hydroxytyrosol derivatives are 61% higher than the stipulated European regulation.

Prokopis Magiatis, Associate Professor at the Athens University Faculty of Pharmacy commented on The Governor™ EVOO:

“..we can certify that [“The Governor”™] is an extremely rare extra virgin olive oil that stands out from the usual oils… It is an oil highly recommended to all consumers looking for olive oil with enhanced properties for health protection.”

The Governor™ website can be viewed here.

The Governor™ EVOO can be bought online from various sources, including:

Olympic Trading, Co.

Elenianna

Amazon

Olympicco