How liver health impacts the risk of Alzheimer’s

While we still do not know exactly what causes the development of Alzheimer’s disease, specialists have been hard at work trying to identify the most salient risk factors. New research has now identified a new player when it comes to Alzheimer’s risk: the liver.
liver illustration
New research highlights the liver’s potential role in raising the risk of Alzheimer’s.

This week, at the yearly Alzheimer’s Association International Conference — held in Chicago, IL — researchers led by Dr. Mitchel A. Kling, an associate professor of psychiatry at the University of Pennsylvania in Philadelphia, have presented the intriguing findings of their latest study.

They observed that Alzheimer’s disease risk is associated with reduced levels of plasmalogens, a type of phospholipid produced in the liver. They play key roles in maintaining the health of brain cells.

From the liver, plasmalogens are carried to the brain and other organs through the blood. Levels of these phospholipids can be measured through specialized tests that have been devised by Dr. Kling in collaboration with colleagues from the Alzheimer’s Disease Metabolomics Consortium at Duke University in Durham, NC.

The researchers identified three indices — assessing the ratios of different plasmalogens to each other, the ratios of plasmalogens to other lipids, and a combination of these measurements — that allow them to determine the amount of plasmalogen as it relates to cognitive functioning.

Specifically, they were interested in confirming whether decreased plasmalogen levels were linked with an increased risk of developing various degrees of cognitive impairment, including: Alzheimer’s disease, mild cognitive impairment (MCI), or significant memory concerns (SMC).

Changes in the liver influence risk

Dr. Kling and team assessed the levels of several different plasmalogens, including ones containing specific omega-3 fatty acids: docosahexaenoic acid (DHA), and eicosapentaenoic acid. They also measured the levels of one omega-6 fatty acid, and of some nonplasmalogen lipids closely related to plasmalogens.

The measurements were taken in samples of blood-based bodily fluids collected from two different groups of study participants.

The first group was made of 1,547 people diagnosed with Alzheimer’s disease, MCI, or SMC, as well as a number of people confirmed to be cognitively normal. These participants were enrolled in the Alzheimer’s Disease Neuroimaging Initiative.

The second group was made of 112 individuals with Alzheimer’s or MCI, or who were considered cognitively normal. These latter participants were recruited via the Penn Memory Center.

Dr. Kling and colleagues saw that lower values of the indices they measured corresponded to a higher risk of developing Alzheimer’s, and a similar association was observed for MCI diagnoses.

Moreover, the scientists also noticed that decreased levels of certain plasmalogens appeared to be linked with heightened levels of the tau protein, which is a hallmark 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,” notes Dr. Kling.

This research […] 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.”

Dr. Mitchel Kling

“This could lead to the eventual destruction of the peroxisomes [functional elements within cells] that create plasmalogens which thus, increases the risk of Alzheimer’s.”

A ‘promising’ journey of discovery

These observations, the team adds, might also explain why Alzheimer’s patients who receive fish oil or supplementary DHA do not show any improvement of cognitive function.

This may happen because the liver is unable to integrate the fatty acids into the plasmalogens.

Another intriguing notion is the fact that certain genes thought to play a role in Alzheimer’s disease also regulate the transport and metabolism of lipids, so researchers are now interested in finding out whether this has any bearing on the relationship between lipid production and brain health.

“Our findings provide renewed hope for the creation of new treatment and prevention approaches for Alzheimer’s disease,” Dr. Kling explains. “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,” he adds.

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