Liver could contribute to Alzheimer’s risk by failing to supply key lipids to the brain

One of the reasons for onset of Alzheimer’s disease is found to be the reduced levels of plasmalogens—a class of lipids created in the liver that are integral to cell membranes in the brain, according to new research presented at the Alzheimer’s Association International Conference (AAIC), 2018.

Plasmalogens are created in the liver and are dispersed through the blood stream in the form of lipoproteins, which also transport cholesterol and other lipids to and from cells and tissues throughout the body, including the brain.

Researchers 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.

This research shows that an age-related deficiency of plasmalogens could lead to an increased risk of Alzheimer’s disease, because the liver cannot make enough of them. It also highlights a potential relationship between conditions such as obesity and diabetes and Alzheimer’s—as the liver has to work harder to break down fatty acids over time. This could lead to the eventual destruction of the peroxisomes that actually create plasmalogens, increasing the risk of Alzheimer’s.

Additionally, some of the decreased plasmalogen levels were correlated with increased levels of the tau protein in the brain, a marker of Alzheimer’s disease.

Lack of effect of fish oil or DHA is also 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 genes associated with Alzheimer’s are involved in lipid transport or metabolism, therefore ongoing research is focused on changes in the production or transport of lipids and how it affects brain structure and function.

Findings provide renewed hope for the creation of new treatment and prevention approaches for Alzheimer’s disease, as researchers examine the connections between plasmalogens, other lipids, and cognition, in addition to gene expression in the liver and the brain, to discover how liver, lipids, and diet are related to Alzheimer’s disease and neurodegeneration.

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