I am the first and only scientist to solve the biochemical mechanism and cause of reduced cognition – a deficiency of plasmalogens in the synaptic membrane of cholinergic neurons leads to a reduced uptake of choline following a neuron firing event. Reduced synaptic choline uptake results in excessive de novo intracellular choline synthesis via methyltransferase activity (which causes elevated homocysteine) and membrane catabolism (which causes cell shrinkage) to sustain sufficient acetylcholine levels for nerve transmission. Using data from multiple independent international clinical research collaborators I published data supporting this mechanism and cause in 2007. From 2007, I developed, tested, and validated various biochemical precursor technologies capable of selectively and specifically elevating plasmalogens and was awarded multiple diagnostic and synthetic chemistry patents related to this work. In 2021, I proved that my hypothesis was correct by administering a plasmalogen precursor that I specifically designed for improved synaptic neurotransmitter release to twenty-two persons diagnosed with cognitive impairment. In less than four months, a statistically significant improvement in cognition was observed.
To access the FREE seminars with full presentations and videos please visit Dr. Goodenowe’s resource site here. This is the article for Lecture 3 – The Biochemistry of Cognition: Breaking Alzheimer’s – The Definitive Lecture Series.
In Lecture #3 – The Biochemistry of Cognition of the Definitive Lecture Series, I present and explain the science so everyone can understand how cognition works, how it fails, and how and why plasmalogen supplementation works. Specifically, in the lecture, you will learn:
- How the prevalence and severity of cognitive decline increases with increasing age
- That approximately 60% of persons over 90 are cognitively impaired
- That reduced cognition is an independent risk factor for all-cause mortality
- That impaired cholinergic neuron function is a prerequisite to cognitive decline
- The synaptic availability of acetylcholine is directly related to and causal to cognition
- The density of acetylcholine neuron terminals is directly related to and causal to cognition
- Presynaptic neuron acetylcholine synthesis and release during neuron transmission is dependent upon sufficient local choline availability
- The primary source and mechanism to recharge presynaptic acetylcholine levels is choline uptake from the synapse via the choline high affinity transporter (CHT)
- Inhibition of the CHT dramatically reduces the ability of acetylcholine neuron to maintain stimulated acetylcholine release
- Reduced CHT activity initiates intracellular membrane auto-cannibalism to maintain choline availability for acetylcholine
- Auto-cannibalism is active in Alzheimer’s brain
- Ethanolamine plasmalogens have unique membrane fusion enabling properties
- Membrane fusion efficiency is dependent upon the concentration of DHA containing plasmalogens in the membrane
- Membrane fusion is the biophysical process through which CHT is expressed on presynaptic membranes
- That plasmalogen levels are decreased in brain samples of persons with dementia
- Plasmalogen deficient animals exhibit reduced acetylcholine neurotransmitter release
- Deficient DHA-plasmalogens in the brain is the primary cause of reduced cognition
Cognition is and has always been of great interest to humans. A great deal of philosophical and biochemical research has been performed on this topic. However, it was not until the mid to late 1970s that specific biochemical and neuroanatomical abnormalities were directly associated with Alzheimer’s neuropathology and reduced mental function. Researchers compared the biochemical activity of different enzymes involved in the biosynthesis of different neurotransmitters. The biochemical system that was observed to be selectively impaired in Alzheimer’s disease and dementia was the acetylcholine neuron system. This discovery clarified earlier observations that anticholinergic drugs could induce dementia in the elderly in the 1960s. These observations spurred a flurry of research into the cholinergic system and its role in cognition and dementia. We now know a lot of detailed information about the acetylcholine neuron system in the brain and its role in cognition. All the reams of data accumulated since then have not changed a simple fact: reduced mental function is caused by a reduction in acetylcholine neuron transmission — period.
I call plasmalogens the lipid of life because plasmalogens are the key to your brain’s quantum mechanical powers. The essence of your brain is the connectivity and communication of your neurons. When you verbally communicate with another person, your vocal chords transmit a sound wave. The other person receives the sound wave in their ear. This is the equivalent of two neurons talking to each other. However, neurons do not use sound waves to communicate, they use neurotransmitters. Instead of using vocal chords to create and transmit a sound wave that travels between two people in the air, neurons spit out packets of neurotransmitters that travel between two neurons in a gap between the two neurons called a synapse. The neuron doing the talking is called the presynaptic neuron and the neuron doing the listening is called the postsynaptic neuron. The talking neuron stores pre-packaged neurotransmitters in neurotransmitter containers called vesicles. When the talking neuron wants to speak, it has to spit its neurotransmitters into the synapse. This is a biophysical process where the vesicle has to fuse to the presynaptic membrane and release its contents. At this instance, the phospholipids of the membrane and the phospholipids of the vesicle must be able to mix together to form a new membrane in a process called membrane fusion. The physical process of membrane fusion involves a transition phase called an inverse hexagonal phase. One of the special powers of plasmalogens is the ease at which they can form an inverse hexagonal phase – better than any other phospholipid in the body. The formation of this phase is a prerequisite for two phospholipid bilayers to fuse into one membrane. This occurs at the very instance that a presynaptic vesicle (which contains the neurotransmitters) touches the presynaptic membrane. This is the biophysical process of neuron transmission. It is the most basic function of the brain – required of all neurons of all types. It is the biological equivalent of flipping a light switch on and off, which sounds simple enough in the abstract. It is the scale at which the brain performs these functions that is difficult to grasp.
The human brain contains approximately 100 billion neurons. To put that in context, if each neuron were a grain of sand, the number of neurons in the brain would be roughly equal to filling a small swimming pool (10’ x 15’ x 5’) or 750 gallons with sand. Each neuron sends out 7000 dendrites that make synaptic connections with other neurons. That is seven quintillion synapses. Now, if each synapse were a grain of sand, this would be equivalent to 20 football fields (100 yards by 50 yards), all filled by about 6’ of sand. At each of the neuron terminals, the presynaptic neuron bouton contains about 130 synaptic vesicles. These vesicles contain the neurotransmitters that are released every time a neuron transmits its signal. Again, using our sand analogy, the number of vesicles is then slightly more than the total volume of concrete used to make the Hoover dam. The neuronal firing rate for the human brain ranges from 10 to >100 times per second. So, imagine every grain of sand in the Hoover dam, bursting and then reforming itself 10-100 times every second of every day of every year of your life. That is occurring in your brain as you read this. Now, let’s put this computing power in perspective. A typical high-end computer used by gamers has a clock speed of four Gigahertz — four billion events per second. The average clock speed of the human brain ranges from seven to 70 million Gigahertz. All the computers sold globally annually have approximately the combined computing power of one human brain. It is this massive quantum computing power that enables your brain to hover between reality and non-reality and your consciousness to push it one way or another through thought.
Your brain can only maintain this level of activity if it has sufficient levels of plasmalogens in the synapse to enable the fusion of presynaptic vesicles with the synaptic membrane and release of their neurotransmitter load and sufficient levels of plasmalogens in the myelin sheath to enable signal transmission from one neuron to another. This process is the most basic of all physiological processes and common to all neurons in the human brain. It is independent of the type of neuron, neurotransmitter, or postsynaptic receptor.
In Lecture 3 – The Biochemistry of Cognition, Dr. Goodenowe explains the relevant research and literature relating to the biochemistry of cognition. The lectures integrate Dr. Goodenowe’s own research and over 50 years of research from leading researchers from around the world.