Enhances Blood Brain Barrier Function​

• potential role in preventing MCI conversion to AD and related dementias   

• consumption of EVOO is expected to stop and/or slow the progression of AD

• Oleocanthal-rich EVOO restored the BBB function and reduced AD-associated pathology by reducing neuroinflammation through inhibition of NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome and inducing autophagy through activation of AMP-activated protein kinase (AMPK)/Unc-51-like autophagy activating kinase 1 (ULK1) pathway

• oleocanthal significantly decreased amyloid load in the hippocampal parenchyma and microvessels. This reduction was associated with enhanced cerebral clearance of Aβ across the blood-brain barrier (BBB)

• Oleocanthal-low EVOO demonstrated a beneficial effect against Aβ-related pathology in 5xFAD mice, EVOO rich with Oleocanthal-could provide a higher anti-inflammatory effect by targeting multiple mechanisms.  EVOO could prevent, halt progression, and treat AD

• significant increase in (125)I-Aβ40 degradation as a result of the up-regulation of Aβ degrading enzymes following oleocanthal rich EVOO.  There is a  reduced risk of AD associated with oleocanthal rich EVOO could be mediated by enhancement of Aβ clearance from the brain

• EVOO and ROO significantly reduced blood Aβ42/Aβ40 and p-tau/t-tau ratios, suggesting that both altered the processing and clearance of Aβ. In conclusion, EVOO and ROO improved CDR and behavioral scores; only EVOO enhanced brain connectivity and reduced BBB permeability, suggesting EVOO biophenols contributed to such an effect

Long-term intervention with HP-EH-EVOO successful regardless of Genetic predisposition (APOEɛ4)

oleocanthal can reduce the accumulation of β-amyloid proteins via up-regulation of P-glycoprotein and LRP

Oleuropein has been found to reduce levels of beta-amyloid

EVOO could prevent, halt progression, and treat AD

may slow the progression of Alzheimer’s by up to 40%

Oleuropein is a promising plant molecule useful against amyloid diseases

Inhibition of COX activity 

Regarding acute brain injury, High Phenolic EVOO have been shown to counteract stroke and spinal cord injury: hydroxytyrosol, tyrosol and oleuropein demonstrated to reduce infarct volume, apoptosis and ameliorate the outcome of these injuries.  Only oleuropein has been investigated in relation to spinal cord injury and its protective effect has been ascribed to its ability to reduce inflammation.

interference with amyloid aggregation (in vitro)

Anti-aggregation activities on tau protein (in vitro) 

Enhancement of Aβ clearance from the brain (animal model) 

Counteraction of hypoxic brain damage (ex-vivo model)

Attenuates Aβ induced inflammation (animal model)

Beneficial effects on insulin resistance associated with AD

Protection against DA- or 6-OHDA-induce cell death (in vitro)

Counteraction of oxidative stress at brain level 

Induction of autophagy at micromolar concentration

Reduction of cerebral infarct volume after cerebral ischemia/reperfusion injury in mice

Reduction of inflammatory biomarkers (TNF-α, IL-1α, iNOS, COX-2) after spinal cord injury (animal model) 

Reduction of Aβ42 deposition and plaque deposit (animal models)

Counteraction of pE3-Aβ production

Reduction of oxidative stress and apoptosis induced by 6-OHDA (in vitro) 

oleocanthal and ligstroside protect against mitochondrial dysfunction in models of early Alzheimer's disease and brain ageing

affecting the speed of processing, working memory, conceptual reasoning and executive functions hydroxytyrosol and resveratrol, seem to be able to delay and modulate the cognitive brain aging processes and decrease the occurrence of its effects on the brain

Oleocanthal improved clearance of the amyloid beta protein from neurons and reduced the inflammation of astrocytes

Oleuropein prevents the growth of toxic Aβ 1–42 oligomers and blocks their successive growth into mature fibrils following its interaction with the peptide N-terminus, while HT speeds up harmless fibril formation.  EVOO can possibly prevent AD and be used as therapy.

Oleuropein prevents the toxic aggregation of both amyloid beta and tau, proteins that are involved in Alzheimer's 

The pleiotropic beneficial intervention of olive oil intake on the Alzheimer's disease onset via fibrinolytic system

Changes in plasma contact activation and the fibrinolytic system may contribute to vascular dysfunction, inflammation, coagulation, and cognitive impairment in AD. Given this evidence, we propose novel therapies that may, alone or in combination, ameliorate AD progression in patients

Plasmalogen precursor analog treatment reduces levodopa-induced dyskinesias in parkinsonian monkeys

data demonstrate that treatment with a plasmalogen precursor is capable of protecting striatal dopamine markers in an animal model of Parkinsons

The plasmalogen precursor analog PPI-1011 reduces the development of L-DOPA-induced dyskinesias in de novo MPTP monkeys

protective response of oleic and docosahexaenoic acid (DHA)-containing plasmalogen precursors suggests that the neuroprotection observed is not only due to DHA but to the oleic substituent and the plasmalogen backbone.

results suggest that PPI-1011 has neuroprotective and anti-inflammatory properties in the gut and indicate its potential utility as a treatment for both early and more advanced stages of Parkinsons

oleocanthal is biochemically transformed to novel products in amino acids/glycine-containing fluids, which were successfully monitored in vitro and in vivo, creating a completely new perspective to understand the well-documented bioactivities of oleocanthal 

HTyr is neuroprotective by restoring insulin signaling damaged by Aβ25–35 treatment

HTyr and Oleuropein after exposure to Aβ, activate autophagy preventing ROS results support the idea that EVOO polyphenols act synergistically in autophagy modulation against neurodegeneration

HTyr restores mitochondrial energetic deficit

Oleuropein HTyr prevents amylin aggregation

Oleuropein reduces amyloid-β aggregation and increases lifespan

Oleuropein (12.5 mg/Kg) reduces Aβ plaque and restores cognitive performance

Oleuropein prevents amyloid-β deposition, in cortex and hippocampus; restores LTP

HTyr enhances ATP production; ligstroside enhances mitochondrial respiration

Oleuropein also can relieve diabetes complications including diabetic nephropathy, diabetes cardiovascular complications, diabetic retinopathy, poor wound healing, diabetic neuropathy, and diabetic testicular dysfunction. Oleuropein reverses cell apoptosis, regenerates tissues, restores the histological organization, and decreases oxidative stress in treating diabetes complications. Taken together, oleuropein is a promising compound for diabetes and diabetes complicationsmanagement and can be used as a nutraceutical to fight against these diseases