Reversing Alzheimer’s: Causes and Forgotten Cures 

This summary, from a 2025 article by “A Midwestern Doctor,” critiques the conventional approach to Alzheimer’s disease (AD) and outlines alternative, forgotten therapies that address root causes.

This summary is a deep dive for science nerds who want to drink out of the fire hose from current health professionals who have figured out AD on a much deeper level than the current allopathic medical system.

If this feels overwhelming, then click here to see my post on my 5 simple steps to prevent and even reverse AD (and other forms of dementia). Get going on those things, and down the road, if you want more information to go even further, and drink out of that fire hose, then certainly come back to this, and it won’t be so overwhelming because you will be doing the most important things already.

Conventional Flaw and Alternative View

• Conventional Focus Flawed: Decades of AD research focusing on eliminating amyloid plaques (a symptom) rather than the actual cause has left the disease “incurable.” Amyloid-targeting monoclonal antibodies offer minimal benefit with significant side effects (brain bleeding/swelling).
• Amyloid as Protective Mechanism: The amyloid protein is suggested to be a protective mechanism that the brain uses against stressors, making attempts to eliminate it doomed to fail.
• AD is Multifactorial: AD is not a single disease but has multiple subtypes, each requiring tailored treatment (Dale Bredesen’s protocol). AD results from the loss of signals sustaining brain cells and the dismantling of connections, outweighing the formation of new ones.

The Six Subtypes of Alzheimer’s (Bredesen’s Model)

This model identifies six key types of AD, often overlapping, based on their primary triggers:

• Type 1 – Inflammatory: Driven by chronic inflammation (e.g., insulin resistance, poor diet, leaky gut, latent infections). Leads to protective neuronal “downsizing.”
• Type 1.5 – Glycotoxic: Caused by insulin resistance and chronic high blood sugar, resulting in inflammation, trophic deficiencies, and accumulation of Advanced Glycation End Products (AGEs).
  • Note: High insulin levels promote amyloid formation because the breakdown enzyme is shared.
• Type 2 – Atrophic: Caused by deficiencies in essential nutrients, hormones, and trophic factors (supportive signals).
  • Note: Often linked to poor circulation, which reduces nutrient delivery to the brain.
• Type 3 – Toxic: Results from exposure to toxins (biotoxins, heavy metals, industrial chemicals) or chronic infections (e.g., Herpesviruses, Lyme, dental bacteria). Often occurs earlier (40s-60s) with psychiatric/executive dysfunction symptoms.
  • Pharmaceutical avoidance of certain blood pressure meds, statins, acid reflux meds, and sleeping pills for brain health is usually prudent.
• Type 4 – Vascular: Chronic restriction of cerebral blood flow from vascular diseases leads to neuronal injury. Affects processing speed/attention more than memory alone.
• Type 5 – Traumatic: Caused by severe or repeated head trauma (concussions), setting off a chronic degenerative cascade.

Impaired Fluid Circulation and Sleep

• Circulatory Impairment as Primary Trigger: Many successful dementia treatments conclude that the disease stems from impaired blood flow to the brain and/or lymphatic/venous drainage from it.
  • Zeta Potential: Restoring physiologic zeta potential (the dispersal force that prevents aggregation in fluids) is crucial, as it naturally declines with age and affects amyloid folding/clumping.
  • Drainage Procedures: Surgeries to increase lymphatic drainage (China) or venous drainage (American procedure) have shown improvements in neuroimmune disorders.
• Glymphatic System and Sleep: Waste clearance (including amyloid) occurs via the glymphatic system, which primarily functions during deep sleep.
  • Consequence: Poor sleep is extensively linked to dementia (increased risk by 22% to 139%) and accelerates amyloid accumulation.
  • Note: Sleeping pills disrupt restorative sleep and significantly increase dementia risk (17% to 84%).

Cellular Degeneration and Regenerative Therapies

• Neuronal Adaptability: The brain constantly adapts by reinforcing needed circuits and pruning others. AD shifts the balance toward elimination.
• Cell Danger Response (CDR): Cells under stress enter a defensive state where function (e.g., mitochondrial respiration) declines. Many chronic diseases, including AD, result from cells being trapped in this degenerative cycle.
• Integrated Stress Response (ISR): Age-related decline in protein synthesis and accumulation of misfolded proteins can activate the ISR, which decreases protein synthesis and may contribute to cognitive decline.

DMSO (Dimethyl Sulfoxide)

• Mechanism of Action: DMSO possesses unique properties that restore normal circulation, protect cells from stressors, and revive cells trapped in the Cell Danger Response (CDR).
• Reported Efficacy: Numerous anecdotal reports and corroborated animal studies suggest DMSO can effectively treat and reverse dementia and prevent associated neuronal/memory loss, similar to its benefits for strokes and brain injuries.

More on Dimethyl Sulfoxide (DMSO) and Neurological Function

Dimethyl Sulfoxide (DMSO) is an organic solvent with a wide range of biological activities, suggesting its efficacy as a neuroprotectant, especially in the context of brain injuries and neurological disorders such as Alzheimer’s disease (AD).

Proposed Mechanisms in Neuroprotection and AD

• Circulation and Cell Health: As noted in the source text, DMSO’s efficacy stems from its ability to restore normal circulation and revive cells trapped in the Cell Danger Response (CDR), a primitive metabolic state linked to chronic disease.
• Neurotransmitter Modulation: Studies in C. elegans models of AD (A$\beta$-induced paralysis) suggest that DMSO delays paralysis by modulating Glutamate and Acetylcholine neurotransmission. Specifically, it may affect Ca2+ ion permeability, which is essential for neurotransmission.
• Antioxidant and Anti-Inflammatory Effects: DMSO is recognized for its antioxidant properties, acting as a hydroxyl radical scavenger. In models of Traumatic Brain Injury (TBI), DMSO has demonstrated a neuroprotective effect by boosting the body’s endogenous antioxidant enzyme systems (like SOD, CAT, and GPX) to quench Reactive Oxygen Species (ROS), thereby improving cognitive function. It also has known anti-inflammatory and anti-edema properties.
• Blood-Brain Barrier (BBB) Permeability: DMSO is amphiphilic and can cross the BBB. At certain concentrations, it can reversibly open the BBB, a property sometimes utilized to enhance the delivery of other compounds into the brain, though the mechanism is complex.
• Amyloid/Plaque Management:
  • Animal studies show DMSO can prevent neuronal and memory loss resulting from experimentally induced AD or reduced cerebral blood flow.
  • In human trials on patients with “probable AD,” treatment with DMSO reportedly led to a reliable decrease in the severity of mental-amnestic disturbances and a stabilizing influence on the blood-brain barrier.
• Cell Survival: DMSO may prevent neuronal cell death caused by glutamate excitotoxicity and helps protect cells from lethal stressors, which is crucial in regenerative medicine.

Key Technical Considerations

• Dose-Dependent Effects: The biological effects of DMSO are highly dose-dependent, and this is a critical factor in its application:
  • Low Concentrations (e.g., 0.01% to 0.1%): May exhibit a hormetic, cytoprotective, or growth-promoting effect on certain brain cells, and has shown therapeutic potential in prodromal AD models.
  • Higher Concentrations (e.g., ≥2% in in vitro or high mL/kg doses in vivo): Can be cytotoxic and cause effects like neuronal apoptosis (especially in the developing central nervous system) or hypothermia in animals.
• Tau Protein: In mouse models, high doses of DMSO (4 mL/kg) caused tau hyperphosphorylation, an AD hallmark, but this effect was found to be indirect, resulting from the drug-induced hypothermia, as maintaining the animals’ normothermia prevented the effect. Direct hyperphosphorylation was also observed in vitro at low concentrations in some cell lines.
• CNS Stem Cells: A concentration of 1% DMSO has been shown in vitro to robustly suppress oligodendrogenesis (the creation of myelin-forming cells) in favor of astrogenesis, a finding that calls for caution in its use, especially in cell transplantation for demyelinating diseases like Multiple Sclerosis (MS).

These properties highlight DMSO as a versatile and potent molecule for neurological applications, but one whose efficacy and safety are closely tied to the specific concentration, administration method, and biological context. For dosing and administration of  DMSO, it is crucial to find a functional medicine professional who is well-versed in its use.

The Bredesen Protocol (ReCODE/PreCODE)

The Bredesen Protocol, often referred to as ReCODE (Reversal of Cognitive Decline) or PreCODE (for prevention), is a comprehensive, personalized, and multi-factorial therapeutic approach to addressing cognitive decline and Alzheimer’s disease (AD). It moves away from the single-drug amyloid focus toward treating AD as a chronic condition with multiple underlying causes.

Foundational Scientific Premise

• APP as a Master Switch: The protocol is based on the idea that Amyloid Precursor Protein (APP) is a master switch for synaptic organization. When the brain has sufficient trophic factors (growth factors, hormones, nutrients, energy), APP is cleaved into two “synaptoblastic” peptides, supporting synapse production and maintenance (plasticity).
• The Downsizing Mechanism: When the brain is under chronic stress from insults (inflammation, toxins, infections), APP is cleaved into four “synaptoclastic” peptides, which mediate synapse loss, neuronal programmed cell death, and simultaneously act to fight the insult (e.g., encapsulating pathogens with amyloid).
• Fixing the Holes in the Roof: The goal of the protocol is to reverse this imbalance—the downsizing of synaptic density—by identifying and addressing all the specific insults, which Dr. Bredesen analogizes to patching the 36 “holes in the roof” that are driving the decline in an individual.

Core Components and Personalization

The protocol requires extensive initial evaluation, known as a “Cognoscopy,” which includes:

1. Advanced Diagnostic Testing: Analysis of over 150 variables/biomarkers, including:
   • Genetics: Especially ApoE4 status.
   • Metabolic Markers: Fasting insulin, HOMA-IR, HbA1c, and lipid panel.
   • Inflammatory Markers: High-sensitivity C-Reactive Protein (hs-CRP), IL−6.
   • Nutrient/Hormone Status: Vitamin D, B vitamins, thyroid hormones (T3/rT3), cortisol, sex hormones (e.g., estradiol, testosterone).
   • Toxins/Infections: Testing for heavy metals, mycotoxins (mold), and various pathogens (e.g., oral spirochetes).
2. Personalized Intervention: Based on the individual’s specific “type” of Alzheimer’s (Inflammatory, Atrophic, Toxic, etc.) and their lab results, a comprehensive, multi-factorial program is created. The program addresses factors across multiple systems:
   • Dietary Modification: Typically a mild ketogenic, low-glycemic Mediterranean-type diet (often referred to as KetoFlex12/3), emphasizing whole, organic, plant-heavy foods, healthy fats (like olive oil and coconut MCTs), and wild-caught fish (especially SMASH: salmon, mackerel, anchovies, sardines, herring).
     • Fasting: Incorporating a minimum 12-hour nightly fast to encourage ketosis and reduce insulin signaling.
   • Supplements & Nutraceuticals: Targeted supplementation to correct deficiencies (e.g., Vitamin D, B vitamins, Omega−3s) and address specific identified drivers (e.g., detoxification agents, anti-inflammatories).
   • Lifestyle Optimization:
     • Exercise: Regular, high-intensity functional training is often emphasized (X Gym style is ideal).
     • Sleep: Focus on optimizing restorative sleep (improving glymphatic drainage), maximizing deep phase sleep (at least 1 hour), and treating underlying issues like sleep apnea.
     • Stress Management: Techniques to reduce cortisol and chronic stress.
     • Brain Training: Cognitive stimulation and engagement (e.g., platforms like BrainHQ).
   • Detoxification/Infection Management: Interventions to remove heavy metals, treat mold toxicity, and clear chronic infections (e.g., dental bacteria).

Clinical Evidence and Context

The protocol has been reported in case series and non-randomized trials to achieve stabilization or reversal of cognitive decline in patients with subjective cognitive impairment (SCI), mild cognitive impairment (MCI), and early AD. These reports, while promising, have been criticized by some in the mainstream medical community for lacking large-scale, randomized, placebo-controlled trials necessary for definitive validation. However, proponents emphasize that a multi-factorial protocol targeting numerous root causes cannot be effectively tested using the single-variable drug trial model.

Hormonal and Inflammatory Targets in the Bredesen Protocol

The Bredesen Protocol is highly focused on correcting imbalances in two major systems—the endocrine system (hormones) and the immune system (inflammation)—as these are core drivers for the Inflammatory (Type 1), Glycotoxic (Type 1.5), and Atrophic (Type 2) subtypes of Alzheimer’s disease (AD).

1. Hormonal (Trophic) Targets (Addressing Type 2 – Atrophic)

The Atrophic subtype results from a deficiency in trophic (supportive) signals, which are largely provided by hormones and growth factors. The protocol aims to restore optimal levels, not just “normal” lab ranges, of these factors to shift the balance back toward synaptoblastic activity.

• Thyroid Hormones (T3​): Thyroid hormones are critical for neuronal function and metabolism. Low T3​ (even within the “normal” range) can impair brain energy production and lead to cognitive decline.
  • Target: Optimize Free T3​ and evaluate Reverse T3​ (rT3​) to ensure effective cellular utilization, often requiring the treatment of subclinical hypothyroidism.
  • Pro tip: Many people enjoy improved thyroid function with more iodine. This is why I eat organic seaweed squares (Costco), and when I eat them with my salmon salad recipe, tucked inside and eaten like a mini taco, I’m getting iodine and Omega-3 at the same time!
• Sex Hormones (Estrogens, Testosterone, Progesterone): These hormones are powerful neurosteroids that provide trophic support, protect neurons, reduce inflammation, and stimulate neurogenesis. Decline in these hormones is often linked to the Atrophic subtype, especially in post-menopausal women.
  • Target: Some, when necessary, use Bioidentical Hormone Replacement Therapy (BHRT) to restore physiological levels, monitoring carefully for safety and efficacy.
• Vitamin D: Technically a prohormone, Vitamin D is essential for synaptic plasticity and protection against amyloid toxicity.
  • Target: Raise serum levels of 25(OH)D to an optimal range, typically 60−90ng/mL (125−200nmol/L), often requiring high-dose supplementation.
• BDNF (Brain-Derived Neurotrophic Factor): This is a key growth factor that promotes the survival of existing neurons and encourages the growth and differentiation of new ones (neurogenesis).
  • Target: Direct supplementation is not feasible, so BDNF is boosted indirectly through lifestyle factors, particularly high-intensity functional training (like the X Gym methodology), cognitive challenge, and specific compounds like curcumin and Omega−3 fatty acids.

2. Inflammatory Targets (Addressing Type 1 – Inflammatory)

Chronic, low-grade inflammation in the brain (neuroinflammation) is a primary trigger for the protective, synaptoclastic response. The protocol seeks to identify and eliminate the specific, underlying sources of this inflammation.

• Metabolic Inflammation (Glycotoxicity): This is the focus of Type 1.5 AD, driven by insulin resistance, which promotes inflammation and amyloid pathology (as the insulin-degrading enzyme also degrades amyloid).
  • Target: Tight blood sugar and insulin control through the KetoFlex12/3 diet, focusing on low glycemic index foods, eliminating refined carbohydrates, and ensuring a minimum 12-hour nightly fast to drive insulin sensitivity.
• Gut Health and Leaky Gut: Systemic inflammation often originates in the gut. A compromised intestinal barrier (“leaky gut”) allows bacterial products (like LPS) to enter the bloodstream and trigger chronic immune activation, which subsequently inflames the brain.
  • Target: Use probiotics, prebiotics, and specific nutrients (e.g., L-glutamine, collagen) to heal the gut lining, along with eliminating inflammatory foods (like gluten/dairy, based on sensitivity testing).
• Chronic Pathogens and Toxins: Persistent infections and exposure to biotoxins (mold/mycotoxins) cause continuous immune activation that drives neuroinflammation.
  • Target: Aggressive diagnosis and eradication of pathogens (e.g., oral P. gingivalis, HHV−1, Lyme) and biotoxin removal through binding agents (e.g., cholestyramine) and environmental remediation.
• Inflammatory Markers: Systemic inflammation is monitored via biomarkers.
  • Target: Reduce levels of hs-CRP (High-Sensitivity C-Reactive Protein), IL−6 (Interleukin-6), and TNFα (Tumor Necrosis Factor alpha) through diet, supplements (e.g., Omega−3s, curcumin), and treating the root cause (e.g., eliminating the infection).

In essence, the Bredesen Protocol views cognitive decline not as a lack of a single drug, but as a protective reaction to a metabolic or toxic overload, which is corrected by identifying and treating all contributing “subtypes” simultaneously.

The KetoFlex 12/3 Diet: Specific Recommendations

The KetoFlex12/3 diet is a cornerstone of the Bredesen Protocol, designed to address the metabolic and inflammatory components of Alzheimer’s disease, particularly the Glycotoxic (Type 1.5) and Inflammatory (Type 1) subtypes. It combines elements of a mild ketogenic diet, a plant-rich Mediterranean diet, and intermittent fasting.

1. The “12/3” Intermittent Fasting Component

This numerical notation refers to the minimum fasting windows required to optimize metabolic flexibility and induce mild ketosis:

• 12-Hour Overnight Fast: A minimum of 12 hours of fasting is required between the last meal of the evening (dinner) and the first meal of the following day (breakfast). This minimum duration is essential for promoting autophagy (cellular clean-up) and ensuring the liver begins generating ketones, which the brain can use as a superior fuel source.
• 3-Hour Pre-Sleep Fast: A minimum of 3 hours must pass between the last bite of food and bedtime. This prevents high insulin and blood glucose spikes during sleep, optimizing restorative sleep (essential for glymphatic drainage) and promoting a healthy nocturnal fast.

2. “KetoFlex” – Fuel Source and Flexibility

The diet encourages a mild, flexible ketosis rather than the deep, restrictive ketosis of therapeutic diets.

• Focus on Ketone Production: The goal is to train the body to burn fat for fuel, generating ketones. This is achieved by limiting processed carbohydrates and favoring healthy fats.
  • Goal: Maintain ketones in a mild therapeutic range (often 0.5−1.5mM) and avoid excessive glucose spikes.
• Energy Sources:
  • Healthy Fats: Should be the primary caloric source. Emphasis is on monounsaturated fats (like extra virgin olive oil), medium-chain triglycerides (MCT oil, often derived from coconut), avocados, nuts, and seeds.
  • Protein: Intake is moderate—sufficient for maintaining muscle mass (especially important alongside high-intensity training) but not excessive, as high protein can trigger insulin release (mTOR signaling). Sources should be clean, such as wild-caught fish (high in Omega−3s), pastured poultry, and grass-fed/finished beef in moderation.
  • Carbohydrates: Should be complex, low-glycemic, and primarily derived from non-starchy vegetables and low-sugar fruits (especially berries). Starchy vegetables (e.g., potatoes, corn) and grains are minimized or eliminated.

3. Key Food Emphasis and Restrictions

A. Foods to Emphasize (The “Flex” – Plant and Nutrient Rich)

• Non-Starchy Vegetables: Consume a wide variety of colorful, often organic vegetables (e.g., leafy greens, cruciferous vegetables, peppers). These provide fiber for gut health, antioxidants, and essential micronutrients.
• Healthy Fats: Extra virgin olive oil (EVOO) is a staple.
• Wild-Caught Fish: Particularly SMASH fish (Salmon, Mackerel, Anchovies, Sardines, Herring) for high DHA/EPA Omega−3 content, essential for brain structure and function.
• Nuts and Seeds: Raw, unsalted sources like walnuts, pecans, almonds, and flax seeds, in moderation due to calorie density.

B. Foods to Minimize or Eliminate

• Simple Sugars & Refined Carbs: Strictly eliminate all processed foods, sodas, fruit juices, white bread, pasta, and all forms of added sugar.
• Gluten and Dairy: These are typically removed or severely restricted as they are common inflammatory triggers and gut irritants that can lead to Type 1 inflammation.
• High-Glycemic Fruits: Limit high-sugar fruits like bananas, grapes, and tropical fruits. Berries are preferred due to lower sugar content.
• Inflammatory Seed Oils: Avoid hydrogenated and refined vegetable oils (e.g., soybean, corn, cottonseed), which are high in inflammatory Omega−6 fatty acids.

This comprehensive approach targets the key physiological levers (insulin sensitivity, inflammation, and energy source) to starve the neurodegenerative process and support synaptoblastic activity.

The Role of the ApoE4 Gene in Cognitive Decline

The Apolipoprotein E (ApoE) gene plays a critical role in lipid metabolism, transport, and repair within the brain. It has three main alleles: ApoE2, ApoE3, and ApoE4. The ApoE4 allele is the single greatest genetic risk factor identified for late-onset Alzheimer’s disease (AD).

ApoE4 and Risk Factor Assessment

• ApoE3 (The Common Allele): This is the most common and is considered neutral regarding AD risk. It supports efficient lipid transport and is effective at clearing amyloid beta (Aβ).
• ApoE2 (The Protective Allele): This allele offers a slightly protective effect against AD and is associated with the lowest AD risk.
• ApoE4 (The Risk Allele): Having one or two copies of this allele significantly increases the risk for AD and lowers the age of onset.
  • Heterozygotes (ApoE3/E4): Carry one copy and have a roughly 3-fold increased lifetime risk for AD compared to E3/E3.
  • Homozygotes (ApoE4/E4): Carry two copies and have a roughly 10- to 15-fold increased lifetime risk for AD compared to E3/E3.

Mechanisms of Impairment in the Brain

The ApoE4 protein is structurally less stable and less functional than ApoE3 or ApoE2, leading to several problems within the central nervous system:

1. Impaired Amyloid Clearance: ApoE4 is significantly less efficient at clearing the toxic amyloid-beta (Aβ) peptides from the brain. This results in faster plaque accumulation, which is linked to the degeneration seen in AD.
2. Mitochondrial Dysfunction and Energy Crisis: ApoE4 disrupts the normal function of mitochondria, the energy powerhouses of the cell. This impairment reduces the brain’s capacity for energy production, leading to a state of cerebral hypometabolism often observed in AD. This is especially relevant to the Glycotoxic (Type 1.5) subtype, where poor glucose metabolism is already a factor.
3. Blood-Brain Barrier (BBB) Breakdown: ApoE4 expression weakens the integrity of the BBB. A compromised BBB allows inflammatory molecules, toxins, and pathogens from the bloodstream to enter the brain, exacerbating neuroinflammation (Type 1) and vulnerability to toxins (Type 3).
4. Impaired Synaptic Maintenance and Repair: The ApoE4 isoform is less effective at transporting cholesterol and other essential lipids needed for synaptic formation and repair. This directly contributes to the failure of plasticity, aligning with the core degenerative process described in the Bredesen Protocol.
5. Inflammatory Drive: ApoE4 has been shown to induce a greater inflammatory response in glial cells (the brain’s immune cells) compared to the other alleles, accelerating the neuroinflammatory cascade.

The Role in the Bredesen Protocol

For individuals identified as ApoE4 carriers, the Bredesen Protocol implements an even more aggressive and personalized approach, focusing particularly on minimizing the “hits” that the ApoE4 brain is less capable of handling:

• Aggressive Metabolic Control: Extremely strict adherence to the KetoFlex12/3 diet is mandatory to ensure the brain is primarily fueled by ketones, bypassing glucose hypometabolism.
• Vigilant Toxin Avoidance: Carriers must be exceptionally diligent about testing for and eliminating toxins (mold, heavy metals) and chronic infections, given their impaired BBB integrity.
• Targeted Supplementation: Higher doses of specific supplements that support mitochondrial function, BBB integrity, and inflammation reduction (e.g., Omega−3s, DHA, Vitamin D) are often required.

For ApoE4 carriers, the goal is to reduce chronic insults to the point where the brain’s repair capacity, compromised by the gene, can still maintain neuronal health and prevent the shift to the “downsizing” pathway.

Special Considerations for ApoE4 Carriers: Targeted Supplements and Detoxification

Since the ApoE4 gene increases the risk for AD by compromising the integrity of the blood-brain barrier (BBB), driving inflammation, and impairing clearance mechanisms, the Bredesen Protocol prescribes a more rigorous, targeted regimen for carriers.

1. Targeted Supplementation for ApoE4

The supplement stack for an ApoE4 carrier is highly personalized based on their Cognoscopy results, but emphasizes nutrients that specifically counteract the genetic weaknesses:

• Lipid and BBB Support (Must be High Priority):
  • DHA (Omega−3s): Used in high doses. DHA (docosahexaenoic acid) is a fundamental component of neuronal membranes. In ApoE4 carriers, the brain has a greater need for structural fats to compensate for ApoE4’s poor lipid transport and to strengthen the weakened BBB.
  • Extra Virgin Olive Oil (EVOO): High-polyphenol EVOO is strongly encouraged, as it has been shown to support Aβ and tau clearance and enhance BBB function. Click here to see the one PJ uses (and the name is purely a coincidence).
  • Choline: Essential for the synthesis of acetylcholine (a key neurotransmitter for memory) and phospholipids, which comprise the neuronal cell membranes. Sources include pastured egg yolks (lightly cooked to preserve choline).
• Anti-Inflammatory and Aβ Modulators:
  • Curcumin: Used for its potent anti-inflammatory properties and its ability to cross the BBB and prevent both Aβ and tau aggregation. A highly bioavailable formulation is typically recommended (1g once or twice daily).
  • Resveratrol: Increases SirT1 function, a sirtuin protein that regulates cellular health, aging, and mitochondrial function.
• Mitochondrial and Energy Support:
  • BVitamins: Especially L-methylfolate (B9) and methylcobalamin (B12), which are critical for methylation cycles that reduce inflammatory homocysteine levels. ApoE4 carriers often have higher homocysteine, necessitating optimization.
  • Vitamin D: Target levels are optimized (60−90ng/mL) to leverage its neuroprotective and anti-inflammatory properties.
  • Alpha-Lipoic Acid (ALA) and Coenzyme Q10 (CoQ10): Supplements used to directly support mitochondrial function and reduce oxidative stress, which is often heightened in the ApoE4 brain.

2. Enhanced Detoxification Protocols

Given the ApoE4 gene’s link to Type 3 (Toxic) AD due to a less functional BBB and impaired toxin clearance, the detox protocol is intensified:

• Extended Fasting for Autophagy: While the baseline is a 12-hour fast, ApoE4 carriers are strongly encouraged to extend their daily fast to 14 to 16 hours or more. This prolonged fasting is a powerful activator of autophagy (cellular recycling/cleanup) and facilitates the clearance of misfolded proteins like Aβ and tau, which the ApoE4 brain struggles to remove. The specific olive oil mentioned above is beneficial due to its high polyphenol content, but also because of its high concentration of oleuropein, which is a special compound that increases autophagy.
  • Note: Extended fasting (over 12 hours) should only be pursued if the individual is at a healthy, stable weight with strong muscle mass.
• Aggressive Toxin Testing and Removal:
  • Mycotoxin and Mold Treatment: Due to the severe impact of biotoxins on ApoE4 carriers, comprehensive testing (e.g., urine mycotoxin) is essential. Treatment often involves binding agents (e.g., cholestyramine, activated charcoal) and environmental remediation if mold is found in the home or workplace.
  • Heavy Metal Chelation: If heavy metals (mercury, lead) are identified as drivers, a targeted, physician-supervised chelation protocol is initiated, starting with organic, broken-cell-wall chlorella.
• Support for Natural Detoxification:
  • Liver Support: Use of herbs like milk thistle and adequate sulfur-rich vegetables (cruciferous) to support Phase II liver detoxification pathways.
  • Infrared Sauna: Use of infrared sauna therapy is often recommended to promote detoxification through sweating, helping to excrete heavy metals and other xenobiotics.

These focused interventions aim to effectively reverse the genetic predisposition by optimizing the epigenetic environment—the lifestyle and metabolic factors that control how the ApoE4 gene is expressed.

High-Intensity Functional Training, BDNF, and the ApoE4 Brain

High-intensity functional training at the X Gym is directly relevant to optimizing the brain health of ApoE4 carriers and implementing the Bredesen Protocol, particularly by regulating inflammation and boosting Brain-Derived Neurotrophic Factor (BDNF).

These unique methods serve as a multi-modal therapeutic intervention for ApoE4 carriers and AD prevention, simultaneously boosting BDNF for synaptic support while reducing systemic and neuroinflammation, and incorporating mindful movement for additional brain benefits through focus, concentration, nerve myelination, and coordination.

This benefits the overall nervous system, including the brain, especially the motor and prefrontal cortices. This was part of my design, through extensive research over the years, inspired by my own mom, who was diagnosed with early-onset AD in the year 2000 and passed from the disease in 2005.

1. BDNF: The Brain’s Fertilizer

BDNF is a protein that acts as a potent growth factor in the brain. It is vital for:

• Synaptogenesis: Creating new synaptic connections.
• Neurogenesis: Promoting the survival and differentiation of new neurons.
• Plasticity: Enhancing the brain’s ability to learn and form memories.

For the ApoE4 brain, which is predisposed to synaptic failure and neuronal pruning, boosting BDNF is non-negotiable. BDNF acts as the trophic signal (the “fertilizer”) that pushes the APP cleavage toward the synaptoblastic (two-part) pathway, directly counteracting the degenerative “downsizing” that defines the Atrophic (Type 2) subtype.

2. High-Intensity Functional Training (HIFT) as a BDNF Generator

High-intensity training produces BDNF, and mindful movements force concentration and the learning of new movements. The combination of BDNF and learning at the same time is especially powerful for brain health, neuron and synaptic development, and creating new neural networks, myelination, and even new nerve growth.

This isn’t just my theory. Studies consistently show that physical exercise, especially high-intensity interval training (HIIT) and X Gym’s functional, time-efficient, high-intensity model, is one of the most powerful and immediate ways to increase circulating and brain BDNF.

This is why the X Gym group training schedule includes both strength and Xardio classes. This is also why all of our one-on-one members receive free unlimited access to group classes, so they can add more strength or Xardio classes to complement their one-on-one strength workouts.

• Mechanism of BDNF Release: Intense, brief bursts of exercise create metabolic stress and an oxygen debt in the muscle. This stress signals the muscle to release BDNF (which is initially stored in the muscle) and other signaling molecules (myokines) into the bloodstream. Once in circulation, BDNF readily crosses the BBB to exert its protective and growth-promoting effects on the brain.
• Insulin Sensitivity and BDNF Link: HIFT profoundly improves insulin sensitivity in muscle tissue. Since BDNF release and function are linked to healthy insulin signaling, improving peripheral insulin function (via HIFT) indirectly enhances BDNF activity in the brain. This is crucial for battling the Glycotoxic (Type 1.5) subtype.

3. HIFT and Anti-Inflammatory Effects

HIFT directly addresses the Inflammatory (Type 1) component of AD, a factor that is often heightened in ApoE4 carriers:

• Myokines and Anti-Inflammation: When muscles contract intensely, they release myokines like Interleukin-6 (IL−6) and IL−15. While IL−6 can be pro-inflammatory in a chronic state, IL−6 released acutely during exercise acts in an anti-inflammatory manner, especially by inhibiting the release of TNFα and other chronic inflammatory cytokines.
• Reduced Visceral Fat: HIFT is highly effective at reducing visceral adipose tissue. Visceral fat is a major source of chronic, systemic IL−6, which fuels Type 1 neuroinflammation. Reducing this source directly lowers the overall inflammatory burden on the ApoE4 brain.