Lecture 10 – Plasmalogens and the Epidemiology of Alzheimer’s Dementia

Plasmalogens were first discovered in 1924, almost 100 years ago. Peroxisomes, the intracellular organelle where plasmalogens are made, were discovered in 1960. The rare cerebrohepatorenal syndrome called Zellweger’ syndrome was first identified in the mid 1960’s. This is a very serious disease. Children with this disease typically die within 6 months of birth. In 1973 it was discovered that Zellweger’ syndrome was caused by a lack of peroxisomes. In 1979 it was discovered that plasmalogens were exclusively made in peroxisomes and in 1983 it was shown that children with Zellweger’ syndrome had tissue plasmalogen levels less than 10% of the levels in normal children. Later in the 1980’s children with other rare peroxisomal diseases were observed to have very low plasmalogen levels and in one such disease, Rhizomelic Chondrodysplasia Punctata, the clinical phenotype in some children is exclusively due to plasmalogen deficiencies. Relatively recently, in 2014, it was shown that birth defects that only mildly affect plasmalogen biosynthesis can cause RCDP. These clinical experiences exemplify the importance of sufficient plasmalogen levels for human health. 

To access the FREE seminars with full presentations and videos please visit Dr. Goodenowe’s resource site here. This is the article for Lecture 10 – Plasmalogens and the Epidemiology of Alzheimer’s Dementia and Death, of Breaking Alzheimer’s – The Definitive Lecture Series.

In the late 1990’s post-mortem studies began to reveal that plasmalogen levels were selectively depleted in the brain in persons with dementia. These results were confirmed by multiple researchers over the course of a decade. However, the prevailing hypothesis at the time was that persons with dementia were experiencing increased levels of oxidative stress that was being caused by Alzheimer’s pathology.  

In 1999, using ion cyclotron mass spectrometry, Dr. Goodenowe invented and subsequently patented a comprehensive biochemical analysis technology that enabled him to simultaneously measure thousands of biochemicals in biological samples. Using this technology, Dr. Goodenowe built the world’s most advanced mass spectrometry laboratory and applied this technology to a plethora of research studies from gene function analyses to large clinical trials. In 2005, Dr. Goodenowe performed analyses on serum samples collected from persons with varying degrees of cognitive impairment. When he interpreted the data, he discovered that blood plasmalogen levels were decreased in persons with dementia and the severity of the deficiency was correlated to the severity of the dementia. This discovery meant that the current hypothesis regarding the decrease in brain plasmalogens was wrong. A systemic depletion of plasmalogens was causing dementia, not a local pathology-dependent oxidative stress depletion. 

The ramifications of this discovery was then and continues to be now, immense. We are just now starting to see the effects. Independent researchers from around the world have since confirmed these findings. However, at the time, a discovery of this magnitude had to be vigorously validated and confirmed. To do this, Dr. Goodenowe collaborated with multiple clinical research groups from around the world each of which had clinical samples representing a separate unique aspect of Alzheimer’s and dementia research. Dr. John Flax from San Diego had a large and very well characterized cohort of persons with highly resolved cognition measurements. Dr. Larry Sparks from Sun City Arizona had a cohort of persons where he had collected blood samples at time of death and had detailed post-mortem pathology measurements. Dr. Alan Lerner from Case-Western University in Cincinnati had blood samples that were collected from persons with clinical dementia between 0.6-13 years prior to their death and which were pathologically confirmed to have Alzheimer’s at death. Dr. Masatoshi Takeda from Osaka, Japan had blood samples from Japanese persons with and without dementia. In total, comprehensive plasmalogen analyses were performed on over 400 clinically demented and over 350 non-demented persons. These results were published in 2007 in the Journal of Lipid Research. 

Since the publication of these definitive results, Dr. Goodenowe has continued to expand on these findings with larger studies with more detailed longitudinal outcomes such as the relationship with the APOE genotype, the risk of converting from a non-demented status to a demented status and the risk of death. These additional studies are detailed in Dr. Goodenowe’s 2021 book, Breaking Alzheimer’s

So, what is the full story on the relationship between blood and brain plasmalogen levels and cognition, and death? Join Dr. Goodenowe for Lecture 10 – Plasmalogens and the Epidemiology of Alzheimer’s and dementia and find the answers to these questions and many more.  In Lecture 10 – Plasmalogens and the Epidemiology of Alzheimer’s and dementia, Dr. Goodenowe explains the relevant research and literature relating to the relationship between blood and brain plasmalogen levels, dementia, and death. The lectures integrate Dr. Goodenowe’s own research and over 50 years of research from leading researchers from around the world.