Plasmalogen Deficiencies May Be the Entry Point into Alzheimer’s Disease

If you’ve been following my work, you know I’m fascinated by the intersection of biochemistry, neuroscience, and environmental sciences — especially where it impacts CIRS patients.

Today, we’re going to talk about a molecule that might just be one of the earliest “gates” to Alzheimer’s disease: plasmalogens.

This idea isn’t speculation. It’s based on a landmark study by Goodenowe and colleagues (2007), who followed older adults over time and found that low plasmalogen levels can predict Alzheimer’s risk years before symptoms appear — and that this relationship is independent of the usual suspects like amyloid and tau. Their work suggests that plasmalogen depletion may not just be a side effect of Alzheimer’s… it may be a cause.

The study in a nutshell

In a longitudinal analysis, Goodenowe et al. (2007) measured blood plasmalogen levels in a large group of older adults and tracked who went on to develop dementia. Here’s what they found:

• People with the lowest plasmalogen levels at baseline had increased risk of developing Alzheimer’s compared to those with the highest levels — even after adjusting for age, sex, APOE genotype, and other known risk factors.

• Low plasmalogens predicted Alzheimer’s regardless of traditional biomarkers like beta amyloid and tau, suggesting depletion happens before amyloid/tau buildup.

This work reframes plasmalogen depletion from a biochemical curiosity to a potential causal gateway for Alzheimer’s — and one that may be accelerated in CIRS. For both prevention and recovery, protecting and restoring plasmalogens could help keep that gateway closed.

Plasmalogen loss might be one of the first dominoes to fall on the road to Alzheimer’s. If that’s true, restoring them could be a viable prevention or early-intervention strategy.

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Why plasmalogens matter (especially in CIRS)

Think of your cells like little houses. The cell membrane is the roof and walls — flexible enough to adapt, but strong enough to keep you safe.

Most of that membrane is made of phospholipids. Plasmalogens are a special class of these lipids, distinguished by a unique vinyl-ether bond at one end. This bond makes plasmalogens remarkably good at neutralizing oxidative stress before it can damage more vulnerable parts of the cell. In that sense, plasmalogens are your first line of defense and, as such, they:

• Protect other membrane lipids from oxidative damage

• Reinforce myelin, the insulation on nerve fibers

• Store fatty acids like DHA and arachidonic acid for inflammation resolution and repair

• Regulate cholesterol distribution in membranes for proper signaling

• Modulate immune and neurotransmitter pathways

In other words, plasmalogens help maintain tolerance and resiliency to environmental stressors, such as biotoxins from water-damaged buildings.

When plasmalogens become depleted or imbalanced, the brain becomes more vulnerable to chronic inflammation, especially inflammation from microglia, the innate immune cells that patrol in our brains. 

In healthy adults, plasmalogen levels peak in early adulthood, then decline slowly — about 40% lost by age 70.

In CIRS, that drop can be faster and more severe due to chronic innate immune activation, oxidative stress, and peroxisomal dysfunction. This means CIRS patients may be hitting the “plasmalogen threshold” for Alzheimer’s risk years earlier than the general population.

What makes plasmalogens different from other lipid supplements?

You might already be taking fish oil (omega-3s), phosphatidylcholine (PC), or phosphatidylserine (PS). These are all valuable — but they work differently from plasmalogens and in many ways depend on plasmalogens:

Here’s one simple way of thinking about these phospholipid molecules:

Omega-3s, PC, and PS are building materials. These lipids are essential components of the membrane’s structure and function. Plasmalogens are the project managers — they oversee where lipids go, keep them safe from damage, and make sure they’re ready to perform their roles. Without that coordination, the membrane can become disorganized and dysfunctional even if the “parts” are present.

Why you can’t just eat more plasmalogens

Humans can only get significant plasmalogens from breast milk — designed to fuel rapid brain development in infancy. Adult diets offer tiny amounts (some seafood, organ meats), nowhere near enough to reverse deficiency. Most of the dietary sources of plasmalogens are simply not bioavailable.

For adults, plasmalogens are made internally via peroxisomes and the endoplasmic reticulum and sending them out via the liver. In CIRS, both inflammation and toxin exposure can bottleneck this process.

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Plasmalogens and the Shoemaker protocol — timing and context are everything

In CIRS, it is essential to first address the core inflammatory triggers of CIRS following the steps of the Shoemaker protocol:

• Remove the patient from water-damaged exposure.

• Remove recirculating biotoxins via stool using Cholestyramine or Welchol. 

• Treat microbial imbalances like nasal colonization of MARCoNS or an overgrowth of actinobacteria (Propionibacterium/Cutibacterium Acnes or Corynebacterium Tuberculostearicum) in the skin and/or mucosal linings.

If present, some patients may also need to treat chronic infections like Lyme, Bartonella, and parasites, once patients have gone through these foundational Shoemaker steps.

Plasmalogens shine in the repair and optimization phase — once those fires are mostly out. That’s when they can be incorporated into membranes and restore function without being immediately destroyed by oxidative stress.

However, some patients may benefit from earlier use — especially when symptoms like brain fog, neural fatigue, and hyper-sensitivities are severe, or when there is confirmation of brain atrophy per a NeuroQuant report. In those cases, plasmalogens may help buffer ongoing damage even before full management of the initial inflammatory response is achieved.

Supplementing with plasmalogens

Right now, only two products reliably provide bioavailable plasmalogens — both from Prodrome (developed by Dr. Goodenowe himself):

• Prodrome Glia – Targets repair, especially in white matter tracts and myelin.

• Prodrome Neuro – Focuses on reigniting neural firing, improving signal transmission.

Some clinicians start with Glia to insulate the “wiring,” then add Neuro to boost the “signal.” Some CIRS patients can initially experience heightened histamine and anxiety with Prodrome Neuro. This is usually a sign that the patient is not out of the sickened stage and will likely need to continue treating CIRS and/or the microbial/infectious burden. Ultimately, sequencing is often an individualized process.

As far as dosing, Glia is often tolerated well even at high doses. CIRS patients will commonly do loading doses of 100mg per kg of body weight. In patients already diagnosed with a neurodegenerative disease, those doses may be even higher.

Neuro is sometimes better tolerated in smaller and less frequent doses, especially in hyper-sensitive patients. Some patients will report experiencing improved physical and cognitive energy with as little as 450mg (1 capsule) every 2-5 days.

If you’re considering supplementation, work with a CIRS-literate practitioner and coach who understands both the Shoemaker protocol and lipid biology. And remember — in both CIRS and Alzheimer’s prevention, timing is everything.

Work with me 1-on-1 to assess your plasmalogen levels

If reading this makes you wonder “Could I have a plasmalogen deficiency?” — you’re not alone.

One of the most common questions I get from both CIRS patients and clinicians is how to determine whether low plasmalogen levels may be contributing to cognitive decline, fatigue, or other neurological symptoms.

I offer one-on-one consultations for patients who want to explore this question in detail. As a certified interpreter of the Prodrome Scan Kit — the only commercially available, research-grade lab test for plasmalogen levels — I can guide you through your results and place them in the context of your overall brain health and CIRS.

Here’s what that process typically looks like:

1. Plasmalogen Testing with Prodrome Scan Kit

• Measures key plasmalogen species (including DHA- and choline-based forms) as well as related lipid biomarkers.

• Identifies patterns linked to higher risk of Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative conditions.

2. Integrative Interpretation

• I combine your Prodrome results with NeuroQuant MRI volumetrics and GENIE test to build a detailed picture of your neurological resilience.

• This allows us to assess not just where you are now, but also your trajectory — whether your biomarkers suggest stability, improvement, or decline. 

3. Action-Oriented Recommendations

• I identify potential drivers of plasmalogen depletion (e.g., unresolved CIRS triggers, metabolic impairments, oxidative stress) and create a plan to address them.

• If supplementation is warranted, we discuss timing, formulation (Prodrome Glia vs Neuro), and how it fits within the Shoemaker protocol to maximize repair benefits.

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References

Goodenowe, D. B., et al. (2020). Peripheral plasmalogen deficiency: A logical causative factor in Alzheimer’s disease and dementia. Journal of Lipid Research, 61(9), 1320–1335. https://doi.org/10.1194/jlr.R120000870

Braverman, N. E., & Moser, A. B. (2012). Functions of plasmalogen lipids in health and disease. BBA - Molecular Basis of Disease, 1822(9), 1442–1452.

Paul, S., Lancaster, G. I., & Meikle, P. J. (2019). Plasmalogens: A potential therapeutic target for neurodegenerative and cardiometabolic disease. Progress in Lipid Research, 74, 186–195.