Our Liver’s Might be Contributing to Alzheimer’s Risk
Significant headway is being made in Alzheimer’s disease research. This month scientists have discovered a “big bang” of Alzheimer’s disease — the precise point at which a healthy protein becomes toxic but has not yet formed deadly tangles in the brain. Then, further evidence for the role of Herpes virus in triggering the disease’s onset. Now, new research presented this week at the Alzheimer’s Association International Conference (AAIC) 2018, is suggesting that the liver could be contributing to Alzheimer’s risk by failing to supply key lipids to the brain.
Phospholipids known as plasmogens are created in the liver and dispersed through the blood stream in the form of lipoproteins. These lipoproteins also function to transport cholesterol and other lipid to and from cells and tissues throughout the whole body, including the brain.
Researchers wanted to find out whether reduced levels of these lipids in the bloodstream is linked to an increased risk of Alzheimer’s disease, or changes to cognitive function. To do this, 3 indices were developed by Mitchel A. Kling, MD, an associate professor of Psychiatry in the Perelman School of Medicine at the University of Pennsylvania and the Veterans Affairs Medical Center, and the multi-institutional Alzheimer’s Disease Metabolomics Consortium led by Rima F. Kaddurah-Daouk, PhD, at Duke University School of Medicine:
- The ratios of plasmalogens to each other
- The ratios of plasmalogens to their closely-related, more conventional lipid counterparts
- A combination of these two quantities.
Kling and a team of researchers found that lower values of these indices were associated with a higher likelihood of Alzheimer’s disease.
“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,” said Kling, who is also a fellow of the Institute on Aging. “This research has a variety of interesting implications. For example, it 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 create plasmalogens which thus, increases the risk of Alzheimer’s.”
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.
“Our findings provide renewed hope for the creation of new treatment and prevention approaches for Alzheimer’s disease,” Kling said. “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.”