Attenuation of Inflammatory Processes Associated With Alzheimer's Disease After Consumption of Pomace Olive Oil.
Condition: Alzheimer Disease
MeSH terms: Alzheimer Disease
Study type: Interventional

Summary: 
      Alzheimer's disease (AD) is the most common cause of dementia and its prevalence will
      multiply in the coming years, so it is urgent to establish preventive and therapeutic
      measures. AD it is characterized by cerebrovascular and parenchymal accumulation of protein
      deposits enriched in amyloid-beta (Aβ) as a consequence of alterations of the blood-brain
      barrier. More than 60% of plasma Aβ is associated with triglyceride-rich lipoproteins (TRL),
      being higher in subjects with AD. Microglia act as resident macrophages and play a crucial
      role in most neuropathologies, since it is activated after homeostasis impairment in the
      brain, and surrounds amyloid plaques in patients with AD. As a result of microglial
      activation, a large number of pro-inflammatory markers are released, mediated by alterations
      in the redox state, through the generation of ROS by the complex NADPH oxidase.

      In a previous study, the investigators demonstrated in BV-2 cells that artificial TRL are
      capable of activating microglia and trigger an inflammatory process. In addition, the
      investigators showed that some of lipophilic minor components of pomace olive oil
      simultaneously modulate oxidative stress and the inflammatory response in microglia. The
      investigators suggested that these results should be replicated in humans after consumption
      of pomace olive oil.

      Therefore, in the present study we formulate the hypothesis that human TRL are capable of
      activating microglia and that such activation can be attenuated when those particles are
      generated after consumption of pomace olive oil. The results of the study would lay the
      foundation for the start of clinical trials demonstrating the effect of pomace oil in
      reducing the risk of development and progression of AD.
    

Detailed description: 
      In a previous study, the investigators demonstrated that triglyceride-rich lipoproteins
      (TRL), which transport dietary lipid components, are able of activating microglia, which
      could be associated with the state of neuroinflammation in patients of Alzheimer's disease.
      In addition, the investigators also demonstrated that some of the minor fat-soluble
      components of olive pomace oil simultaneously modulate oxidative stress and the inflammatory
      response in microglia, so that these components could have the ability to protect the brain
      from microglial overactivation when transported in TRL.

      In that study, the investigators used artificial TRL that were manufactured ad-hoc in the
      laboratory, in order to be able to test the effect of the compounds both individually and
      together. Now is the time to consolidate the results using human TRL, obtained after the
      consumption of olive pomace oil. The investigators expect that the results of this study will
      reveal that the intake of olive pomace oil can prevent the release of inflammatory markers
      caused by the overactivation of microglia, which could be associated to a reduction in the
      risk of development and progression of Alzheimer's disease.

      Objectives and design

      To test this hypothesis, two specific objectives will be addressed:

        1. To obtain and characterize human TRL obtained after the intake of olive pomace oil.

        2. To evaluate the mitigating effect of the microglial activation by TRL obtained after the
           intake of olive pomace oil.

      The study has been designed as a randomized and crossover trial in the postprandial phase in
      healthy subjects, which will be divided into two groups to which a pomace oil and high-oleic
      sunflower oil will be administered.

      Activities

      The specific objectives set out in the project will be addressed through the execution of the
      activities that are detailed below:

        1. Selection of volunteers and administration of olive pomace oil. 1.1. Obtaining and
           characterizing the experimental oils. 1.2. Recruitment and selection of volunteers. 1.3.
           Clinical trial in the postprandial phase.

        2. Isolation and characterization of human TRL. 2.1. General determinations in blood serum.
           2.2. Characterization of TRL.

        3. Microglial activation in cells treated with human TRL. 3.1. Assays in cell cultures.
           3.2. Analytical determinations. 3.3. Data processing and reporting.
    

Intervention name(s): Experimental meal
Intervention type(s): Other
Intervention description(s): Two dietary oils will be administrated as part of a single experimental meal, for the present is a postprandial phase study.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention