Alzheimer’s Disease Risk Impacted by Liver and Diet

Reduced levels of plasmalogens are associated with an increased risk of Alzheimer’s Disease. Plasmalogens are created in the liver and are dispersed through the bloodstream in the form of lipoproteins.

Three indices have been developed for measuring the amount of these lipids related to cognition, in order to identify whether reduced levels in the bloodstream are associated with an increased risk of Alzheimer’s disease, mild cognitive impairment (MCI), overall cognitive function, and/or other biomarkers of neurodegeneration in Alzheimer’s disease.

Scientists working with their colleagues at the University of Pennsylvania Perelman School of Medicine (Philadelphia, PA, USA) measured: the ratios of plasmalogens to each other; the ratios of plasmalogens to their closely-related, more conventional lipid counterparts; and a combination of these two quantities. They measured several plasmalogens including those containing omega-3 fatty acids docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), as well as an omega-6 fatty acid and closely related non-plasmalogen lipids, in blood-based fluids collected from two groups.

The first group included 1,547 subjects with Alzheimer’s disease, MCI or significant memory concerns (SMC), and subjects who were cognitively normal (CN) and who are enrolled in the Alzheimer’s Disease Neuroimaging Initiative. The second group included 112 subjects from the Penn Memory Center, including those with Alzheimer’s, MCI, and CN. The team observed that lower values of these indices were associated with a higher likelihood of Alzheimer’s disease. A similar pattern was seen with MCI and CN associations. In addition, some of the decreased plasmalogen levels were correlated with increased levels of the tau protein in the brain.

The findings also provide a possible explanation for the observed lack of effect of fish oil or DHA administration on cognitive function or Alzheimer’s disease, which has been shown in other studies. This is due to the defect in the liver that prevents these fatty acids from becoming incorporated into the plasmalogens that are critical for synaptic function in brain, which can affect cognition. Several of the genes associated with Alzheimer’s are involved in lipid transport or metabolism, therefore ongoing research is looking to see how changes in the production or transport of lipids affect brain structure and function.

Mitchel A. Kling, MD, a psychiatrist and a leading author of the study, said, “Our findings provide renewed hope for the creation of new treatment and prevention approaches for Alzheimer’s disease. Moving forward, we’re examining the connections between plasmalogens, other lipids, and cognition, in addition to gene expression in the liver and the brain. While we’re in the early stages of discovering how the liver, lipids, and diet are related to Alzheimer’s disease and neurodegeneration, it’s been promising.” The study was presented at the 33rd Alzheimer’s Association International Conference held July 26-29, 2018, in Chicago, IL, USA.

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University of Pennsylvania Perelman School of Medicine