Oleocanthal Treatment Improves Metabolic and Behavioral Changes in Alzheimer’s Mouse Model Study

Oleocanthal Treatment Improves Metabolic and Behavioral Changes in Alzheimer’s Mouse Model Study

Alzheimer’s disease (AD) is a brain disorder that gradually diminishes memory, critical thinking, and overall cognitive function, eventually leading to the inability to carry out everyday tasks. It is ranked as the seventh leading cause of death in the United States and the leading cause of dementia among older adults. The majority of individuals who develop AD begin to display symptoms later in life, typically after age 65. While this disorder can develop in younger people, aging is considered a major risk factor. 

Animal studies are frequently used to study memory, behavior, and pathology related to Alzheimer’s disease. Researchers were interested to understand if the metabolic changes that happen with age and if there is a potential for phenolic compounds to impact these changes. 

A recent mouse study delved into the complex interplay between aging, Alzheimer's disease, metabolic changes, and behavioral alterations in mouse models. The research had three primary objectives: 

  1. Assessing Changes with Age and Alzheimer's Disease Pathology: The study aimed to evaluate how metabolic and behavioral parameters change with age and AD pathology in both normal (WT) mice and those with AD (5xFAD).
  1. Linking Sleep Disturbances with Alzheimer's Disease: The researchers sought to establish a connection between sleep disturbances, blood-brain barrier (BBB) dysfunction, and brain amyloid-beta (Aβ) levels.
  1. Evaluating the Effects of Oleocanthal Treatment: The study explored how treating 5xFAD mice with oleocanthal (OC) affected metabolic and behavioral parameters.


The study used the Promethion cage systems® to monitor changes in physiological metabolic and behavioral parameters with age and pathology in both wild-type and 5xFAD mouse models. 5xFAD mice possess five genetic mutations that cause them to develop amyloid deposition, gliosis, and progressive neuronal loss accompanied by cognitive and degradation of motor function, similar to what humans with Alzheimer’s exhibit, so they are often used in research of this type.

To assess whether any of these parameters could be altered by treatment with oleocanthal (OC) - a phenolic compound found in extra virgin olive oil that has been shown to have neuroprotective properties - mice were given oleocanthal.

As expected, it was found in this study that metabolic parameters including body weight, energy expenditure, intake of food and water, dehydration, respiratory exchange rate, and behavioral parameters of sleep patterns and anxiety-like behavior were altered by age as well as AD pathology. The effect of the AD pathology on these parameters was significantly greater than what would be seen with normal aging, which researchers believed could be linked to amyloid-β deposition and disruption of the  Blood-Brain-Barrier (BBB).

Their findings also showed an inverse correlation between sleep hours and BBB breakdown. Oleocanthal treatment was also found to reduce anxiety-like behavior symptoms and sleep disturbances. This was noteworthy information to add on to previous studies showing that sleep inefficiency may be related to AD progression and that anxiety may be a risk factor for AD. 

Previous studies from this same lab showed that OC treatment reduced brain Aβ levels, reduced neuroinflammation, improved the blood–brain barrier (BBB) function, enhanced autophagy, and improved memory function. 

In addition to showing associations between aging and AD and changes to metabolism and behavior, this study also reinforced other research showing that oleocanthal could be a valuable tool for improving these factors. This study also showed that monitoring these changes in parameters could offer insight as to AD severity and treatment efficacy in further AD mouse model studies. 

While more research is needed before we can have clear recommendations for how to use oleocanthal as a protective agent, this does provide more evidence for the potential benefits of working oleocanthal-rich extra virgin olive oil into an overall healthy diet.

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