Has a New Cause of Alzheimer's Been "Swept Under the Rug?"

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Written by Susan D. Clark | Updated on June 11, 2021

Reviewed by Susan D. Clark

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Has a New Cause of Alzheimer's Been "Swept Under the Rug?" about undefined
When someone develops Alzheimer's diseases, the brain changes. These changes include more than the growth of telltale plaques. The brain’s cells themselves change, especially their membranes. These membranes lose up to 60 percent of crucial compounds known as plasmalogens. And, according to researchers at Washington University in St. Louis, scientists have mostly turned a blind eye to this process. By doing so, they're overlooking what may be an important key to unlocking a treatment for this devastating, memory-robbing disease. Plasmalogens are types of fat classified as phospholipids. In cellular membranes of the brain and the heart, plasmalogens function as structural factors and affect the signals that are exchanged between cells. Richard Gross, one of the scientists at Washington who's investigated the loss of plasmalogens in cell membranes, doesn't pull any punches when he laments the neglect of research focusing on this aspect of brain dysfunction. "These molecules, plasmalogens, have been swept under the rug because nobody likes to think about them," says Dr. Gross. "(They're) hard to work with. They're susceptible to light, they're stable in only certain solvents, they have a limited lifespan after they're synthesized unless extreme precautions are taken, and they're expensive to make and synthesize." Because plasmalogens are tricky to work with in the lab, the processes by which they are created in the body, put into place within cell membranes as well as how they function has remained unexplored. How they break down and are eliminated – as apparently occurs during Alzheimer's – was also unknown, until recently.

So, What Happens to Plasmalogens? 

A study supervised by Dr. Gross discovered that plasmalogens are split apart when a substance called cytochrome c is released from malfunctioning mitochondria, those little organelles that provide energy to drive cellular activities.1 The study suggests that when the brain is suffering from a buildup of damaging free radicals or oxidative stress, the result is damage to cells and an increase in the amount of cytochrome c which accumulates in brain tissue. As a result, the breakdown of the plasmalogens releases new signaling molecules into the brain. "That was one thing that surprised us," Dr. Gross says. "The second thing that surprised us was the ease (with which the plasmalogen bond is broken)...The implication is that there is probably a lot of plasmalogen (breakdown) that's going on in conditions of oxidative stress." Dr. Gross now wants to further explore how and why plasmalogen loss takes place in people with Alzheimer’s disease. He thinks that as we get older, the build-up of free radicals causes mitochondria to increasingly malfunction and release cytochrome c. Meanwhile, tests at the Perelman School of Medicine at the University of Pennsylvania and the Veterans Affairs Medical Center support the findings of Dr. Gross’s investigation and take his research one step further.

Your Liver Could be the Culprit 

This research found that the liver manufactures plasmalogens in the body which are then transported to the brain and other organs through the bloodstream. In the Pennsylvania research, scientists measured various types of plasmalogens circulating in the bloodstream of people with Alzheimer’s disease, people suffering mild cognitive impairment (MCI)-- a condition that often precedes Alzheimer’s-- and other people who did not have cognitive issues. Their analysis shows that the Alzheimer’s victims had the lowest levels of plasmalogens while the group with no cognitive problems had the highest levels. The folks with MCI had levels of plasmalogens that were in between the two other groups.2 "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," says Pennsylvania researcher Michael Kling. "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 (vesicles in cells) that create plasmalogens which thus increases the risk of Alzheimer's."

Provides New Hope for Treatment Strategies 

This new focus on plasmalogens and the liver offers fresh hope for gaining better insight into what exactly causes Alzheimer’s disease. As I’ve often pointed out, research that has focused on eliminating amyloid beta plaques in the brain to treat Alzheimer’s has been a dismal failure. It’s time to take a more holistic approach and see what’s going on in the entire body to better understand this disease and how we can treat it. For example, Dr. Kling and his team wonder if the reason that fish oil doesn’t seem to help Alzheimer’s patients may be connected to the fact that their livers are not functioning very well and can’t convert the oil’s fatty acids into new plasmalogens that the brain needs. As Rima F. Kaddurah-Daouk, a researcher at Duke University who has studied how liver function may affect Alzheimer’s, observes, "While we have focused for too long on studying the brain in isolation, we now have to study the brain as an organ that is communicating with and connected to other organs that support its function and that can contribute to its dysfunction. The concept emerges that Alzheimer's disease might be a systemic disease that affects several organs including the liver.”3
  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986220/ 
  2. https://pubmed.ncbi.nlm.nih.gov/32715599/ 
  3. https://pubmed.ncbi.nlm.nih.gov/31365104/ 

Susan D. Clark

Susan Clark is an award-winning, Emmy-nominated journalist and author who has written about nutrition, health, and wellness for 27 years. She has developed content for articles, reports, books, videos, and television news segments featuring some of today’s top alternative and integrative doctors. She earned a bachelor of science in broadcast journalism from Texas Christian University. She lives in Los Angeles with her husband, two sons, and numerous pets.

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