Are you ready to make an investment in your health? Recently, I introduced you to plasmalogens and the role they play in optimizing health. Today, I want to take the plasmalogen story a step further. In my research, I uncovered an association between plasmalogens and their role in devastating diseases such as Alzheimer’s. In doing so, I founded the plasmalogen deficiency hypothesis of neurodegeneration and dementia.
The problem is that the simplicity of the plasmalogen hypothesis destroys a lot of more complex theories. It provides an entirely different explanation for the cause of reduced mental function in Alzheimer’s disease versus the amyloid hypothesis of Alzheimer’s disease. Up until recently, it was believed that the amyloid plaque neuropathology observed in Alzheimer’s disease is a toxic causative agent of Alzheimer’s disease. The plasmalogen hypothesis states that the reason amyloid is accumulating in the human brain is that the normal and healthy biochemical processing of amyloid in the brain that occurs when we are young and does not result in the accumulation of amyloid deposits requires that your brain has sufficient plasmalogen levels. Plasmalogen levels become deficient with age and when this happens, the brain cannot process amyloid in a healthy way anymore and it begins to accumulate. That is where the plasmalogen hypothesis, our technology with blood testing, and plasmalogen supplementation come in. It allows us to take a profoundly serious human disease that up until now has had no solution, and tackle it head on using a scientifically validated biochemical mechanism.
When I first discovered the plasmalogen deficiency in Alzheimer’s, I started to investigate all of the different things we know about Alzheimer’s disease. I then asked, “How does the plasmalogen deficiency relate to each of these individual pieces of the puzzle?” We know a lot about Alzheimer’s because it is well documented and is not a new disease. We know at what age most people get it, we also know what parts of the brain are affected. The next step was examining all of the underlying biochemical mechanisms published by other researchers to determine what these mechanisms had in common, recognizing that most of them are valid within the confines of the research studies that they came from. Through this analysis, I realized that the plasmalogen hypothesis was the missing link, and that it unified all of the other data that we have on Alzheimer’s disease pathology and reduced cognition.
The Road to Scientific Discovery
My advanced mass spectrometry technology is what enabled me to discover that low blood levels of plasmalogens were correlated with the severity of dementia and reduced cognitive functioning in Alzheimer’s disease versus people that had normal cognition. These discoveries were not made postmortem; they were made from living patients. Like all scientific discoveries, the first part of the discovery is the association with a disease, and the next step is to find causation. The first thing you see is smoke, and then the challenge is to find the fire and finally the arsonist. In this analogy, amyloid is the smoke, membrane dysfunction is the fire and low plasmalogen levels is the arsonist, but it goes deeper than this.
When I first discovered that these plasmalogens were low in Alzheimer’s disease, my job was to do a systematic analysis to find out if these were just symptoms or a byproduct of oxidative stress in the brain? Is it a bystander watching an accident on the road, or is it involved in the causative process of Alzheimer’s disease? To determine this, I had to look at what we already know about Alzheimer’s. We know that the incidence of Alzheimer’s increases as we get older, as does our risk. We also know that people with Alzheimer’s have certain pathologies in the brain that people without Alzheimer’s don’t have. They have certain protein depositions called amyloid plaques. This was the discovery of Dr. Alois Alzheimer in the early 1900s. The two things he observed were the silver staining plaques in the brain and the neurofibrillary tangles. These are the two hallmarks of Alzheimer’s disease, which was named after him. We also know that the brain physically shrinks in size. After more detailed analysis, in the late 1970s, we learned that there was one specific neurotransmitter system that was most affected in dementia patients – a neurotransmitter called acetylcholine.
I began collaborating with university researchers around the world who had ongoing studies in aging and dementia. One of the first things we found was that as people get older, the number of people with a plasmalogen deficiency increases.
We concluded definitively that there is an age-associated decline in blood plasmalogen levels. This was important because before any biological system can be considered part of the Alzheimer’s causation pathway, it has to show an age-related decline. The decrease in blood plasmalogen levels matched the increase incidence of Alzheimer’s disease. In fact, it was occurring earlier. The next step was to determine biochemical mechanisms of cause and effect. We weren’t sure if Alzheimer’s was causing the low plasmalogens levels, or if the low plasmalogen levels were causing Alzheimer’s.
To do this, I conducted experiments to study the effect of different types of plasmalogens and different concentrations of plasmalogens on key biochemical systems known to be involved in Alzheimer’s disease. These are called structure-activity relationship studies. I needed to know if plasmalogens levels in the membrane change, and what happens to these pathological proteins in the brain called amyloid plaques. What I found in the laboratory, was that by increasing specific plasmalogen levels, amyloid plaque formation decreased. More importantly, the specific plasmalogens that had this activity were the very ones decreased in human brains with Alzheimer’s disease. This was the first evidence of true causation in that the level of plasmalogens in the membranes was causing changes in the amyloid density, not the other way around. I then followed up on this observation and analyzed human brain samples from the Rush University study on aging in Chicago and I was able to conclude that people who had high levels of plasmalogens also had lower levels of amyloid plaque in the brain. I also measured all of the key brain biomarkers reported by other scientists and I compared the relationship between these biomarkers and cognition. Of all the biomarkers studied, the level of plasmalogens in the brain were the most correlated with cognition.
The Rush University longitudinal program in aging is an amazing ongoing study in Chicago headed by Dr. David Bennett. Not only do they have a well characterized postmortem database of individuals who have donated their bodies (including their brains) to science, their database and biobank is full of blood samples and cognitive information about these individuals before their death, and on persons still living. As part of this collaboration, my team measured thousands of longitudinal blood samples over many years. The results were definitive. Persons with high blood plasmalogens had a lower risk of dementia versus persons with low blood plasmalogens. Non-demented persons with high plasmalogens were less likely to become demented in the future versus persons with low blood plasmalogens. Persons with high blood plasmalogens were less likely to die than persons with low blood plasmalogens. We also compared blood levels and brain levels in the same person and showed that persons with low blood plasmalogens had low brain plasmalogens. Clearly, brain amyloid is not oxidizing blood plasmalogens.
We now had powerful evidence that the plasmalogen level in brain membranes are part of the causation pathway in both the formation of amyloid plaques and reduced cognition. Low levels of plasmalogen are causing an increase in amyloid. We now know that as we get older, more people have a plasmalogen deficiency. We have proven in the laboratory that if we increase plasmalogen levels, we decrease amyloid. Also, we analyzed the effect of blood and brain plasmalogens on persons with an increased genetic risk of Alzheimer’s due to the APOE e4 genotype. We found that APOE e4 carriers with high blood plasmalogens did not have an increased risk of dementia – high blood plasmalogens neutralized the genetic risk caused by the APOE e4 genotype. We also found that APOE e4 carriers with high brain plasmalogens, had normal brain amyloid levels. High brain plasmalogens neutralized the genetic risk of high brain amyloid caused by the APOE e4 genotype.
When I realized the importance of the low levels of plasmalogens in relationship to Alzheimer’s, it was a eureka moment for me. Once the plasmalogen story came into play and I realized its association with age; It surprised me that something so obvious had stayed hidden for so long.
What steps are you willing to take to enhance your health and quality of life? Download a short summary on plasmalogens, learn about my upcoming book, or explore my videos on the resources page to learn more about how you can change your perspective on health and aging. You can order a blood test or my supplements at www.prodrome.com