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Alzheimer’s and Neurodegenerative Diseases
Cause and Treatments
This is a subject I know intimately, having studied it extensively over several years. At one point, I was preparing to publish an audiobook on the topic but decided to wait in anticipation of a major breakthrough. While that breakthrough hasn’t yet arrived, I’m encouraged by several promising developments. For me, as for many others, Alzheimer’s and age-related dementia are deeply personal. My sister Elaine passed away from dementia, and the experience left an indelible mark on me.
When you witness a friend or loved one deteriorate into a shadow of the person you once knew—someone who no longer recognizes you, and whom you barely recognize—it leaves a lasting sense of helplessness and dread that is impossible to forget.
Before going into depth regarding Alzheimer’s, I want to provide you with a brief history of the condition. Hopefully you will learn some of the things that I have become familiar with. First, I would like to point out the fact that the moniker “Alzheimer’s Disease” or AD is used loosely to describe this condition and most age-related dementias. It is a name that is easy to remember… In point of fact, until recently, Alzheimer’s disease could not positively be identified until after death, when its specific microscopic features can be viewed. However, new tests that reveal key components are changing that. Regardless, the progression and treatment of the disease is essentially the same for all age-related dementias.
The History of Alzheimer’s Disease
In November 1901, Dr. Alois Alzheimer, a German neurologist, made his first examination of a 51-year-old woman, Auguste Deter, who was experiencing problems with memory and language as well as various psychological problems such as disorientation and hallucinations. These symptoms matched the definition of what was then called dementia, but she was rather young to be displaying them, so he diagnosed her as having “presenile dementia”. Auguste Deter died on April 8, 1906. Since Dr. Alzheimer had never seen another case like hers, he obtained her family’s permission to perform an autopsy on her brain.
When he examined it, he observed extensive atrophy, especially in the cortex—the thin outer layer of grey matter that is involved in memory, language, judgment, and thought in general. When Dr. Alzheimer sampled thin slices of this brain tissue and examined them under the microscope, he observed two types of abnormal deposits inside and in between the nerve cells. These two kinds of deposits—one outside the nerve cells, in modern terminology, “amyloid plaques", and the other inside, now known as “neurofibrillary tangles" made up of what we now call tau proteins.
It is my experience that some people want to learn everything they can about Alzheimer’s. To make this possible, I have embedded hyperlinks in the body of the text, indicated by a heavy underline. By hovering over the underline with your cursor it will reveal a blue link where the cursor becomes a finger. By clicking on the blue section, you will be taken to a different site. (Sometimes this is automatic) These are usually authoritative sites such as NIH. When you finish reading, just close the tab at the top of the page and you will be returned to the chapter.
One final note: To provide the greatest benefit to my readers, I suggest the following: If you are already well-acquainted with the details of Alzheimer’s but know someone who may be at risk of developing it or has already been diagnosed, consider skipping ahead to the section titled “Nutrition.” I firmly believe that nutrition and the use of certain nutraceuticals represent the most effective strategies currently available to combat the onset and progression of this disease.
Most importantly, I highly recommend watching the 40-minute podcast narrated by Dr. Mary Newport, linked at the end of this newsletter. It offers a comprehensive overview of Alzheimer’s, along with evidence-based nutritional treatments that have been shown to be effective. Even better, these approaches come with no risks or adverse effects, regardless of one’s health status.
The Hallmarks of Alzheimer’s Disease
Amyloid-β (Aβ) peptides can form protease-resistant aggregates within and outside of neurons. Accumulation of these aggregates is a hallmark of Alzheimer's disease (AD) neuropathology and contributes to devastating cognitive deficits associated with this disorder. The healthy human brain contains tens of billions of neurons—specialized cells that process and transmit information via electrical and chemical signals. They send messages between different parts of the brain, and from the brain to the muscles and organs of the body. Alzheimer’s disease disrupts this communication among neurons, resulting in loss of function and cell death.
The amyloid protein involved in Alzheimer’s comes in several different molecular forms that collect between neurons. It is formed from the breakdown of a larger protein, called amyloid precursor protein (APP). One form, beta-amyloid 42, is thought to be especially toxic. In the Alzheimer’s brain, abnormal levels of this naturally occurring protein clump together to form plaques that collect between neurons and disrupt cell function. Research is ongoing to better understand how, and at what stage of the disease, the various forms of amyloid influence Alzheimer’s.
Neurofibrillary tangles are abnormal accumulations of a protein called tau that collects inside neurons. Healthy neurons, in part, are supported internally by structures called microtubules, which help guide nutrients and molecules from the cell body to the axon and dendrites. In healthy neurons, tau normally binds to and stabilizes microtubules. In Alzheimer’s disease, however, abnormal chemical changes cause tau to detach from microtubules and stick to other tau molecules, forming threads that eventually join to form tangles inside neurons. These tangles block the neuron’s transport system, which harms the synaptic communication between neurons.
Emerging evidence suggests that Alzheimer’s-related brain changes may result from a complex interplay among abnormal tau and beta-amyloid proteins and several other factors. It appears that abnormal tau accumulates in the soma (neuronal cell body) involved in memory. Beta-amyloid clumps into plaques between neurons (shown in blue). As the level of amyloid reaches a tipping point, there is a rapid spread of tau throughout the brain. These beta-amyloid and tau proteins are the distinguishing factors between Alzheimer’s disease and other age-related dementias that can only be seen in a brain autopsy.
Brain Neuron Showing Amyloid Plaque
In 2010, we knew of just 10 genetic areas associated with Alzheimer’s. Today, thanks in large part to the work of NIH-funded researchers, we know of at least 80 genetic areas associated with this disease. Understanding which genes play a role — and what role they play — may help identify new methods to prevent, delay, or treat dementia.
One well-known gene that influences Alzheimer’s risk is the apolipoprotein E (APOE) gene. The APOE gene is involved in making a protein that helps carry cholesterol and other types of fat in the bloodstream. Problems in this process are thought to contribute to the development of Alzheimer’s. APOE comes in several forms, called alleles (e.g., ε2, ε3).
APOE ε2 may provide some protection against the disease. If Alzheimer’s occurs in a person with this allele, it usually develops later in life than it would in someone with the APOE ε4 gene. Roughly 5% to 10% of people have this allele.
APOE ε3, the most common allele, is believed to have a neutral effect on the disease — neither decreasing nor increasing risk of Alzheimer’s.
APOE ε4 increases risk for Alzheimer’s and is associated with an earlier age of disease onset in certain populations. About 15% to 25% of people have this allele, and 2% to 5% carry two copies.
Each person inherits two APOE alleles, one from each biological parent, meaning people can have one of six possible combinations: 2/2, 2/3, 2/4, 3/3, 3/4, and 4/4. Having two copies of APOE ε4 is associated with a higher risk of Alzheimer’s than having one copy. While inheriting APOE ε4 increases a person’s risk of Alzheimer’s, some people with an APOE ε4 allele never develop the disease. This points to the fact that we still don’t have a complete picture of the disease or the factors that lead to cognitive decline. Research has shown that certain mutations that result in genetic variants prevent AD from manifesting itself may offer a clue to a possible cure.
A NIH-funded study identifies this gene variant as potential drug target while studying an individual at high risk for early-onset AD that remained dementia-free for many years beyond what was anticipated. This research focused on the case of a woman who carried a gene mutation known to cause early-onset Alzheimer’s. However, she did not develop signs of the disease until her seventies, nearly three decades after her expected age of onset. The researchers suspect that she may have been protected because in addition to the gene mutation causing early-onset Alzheimer’s in her family, she also had two copies of the APOE3 Christchurch (APOE3ch) gene variant. Findings of this case study as published in Nature Medicine suggest that two copies of the APOE3ch variant, named after Christchurch, New Zealand where it was first identified, may protect against Alzheimer’s.
Cases like this often provide valuable insights that can pave the way for breakthroughs with profound implications for future treatments. Personally, I find such events thought-provoking, particularly in the context of gene manipulation. Since it is evident that naturally occurring or mutated genes can significantly influence the progression of associated diseases, one can’t help but wonder if improved outcomes might be achieved through targeted genetic interventions.
However, paradoxically, pursuing this avenue of treatment may complicate the process of obtaining regulatory approval. It's important to remember that regulatory approvals require substantial financial investment for rigorous testing, clinical trials, and extensive data collection. These costs are typically borne by conventional funding mechanisms, often relying on the promise of royalties from patents. Unfortunately, this tends to favor the development of proprietary, synthetic substances by large pharmaceutical companies, rather than focusing on naturally occurring compounds—such as peptides—where funding for large-scale scientific studies is frequently limited or unavailable.
Genetic Variants Associated with Alzheimer’s Disease
Of the genetic variants so far associated with Alzheimer’s, three rare single-gene variants are known to cause the disease:
Testing for Alzheimer’s
There are accurate blood tests for Alzheimer's disease, and they may be a major step towards making Alzheimer's diagnosis more accessible:
ptau-217 blood test - This blood test is comparable to FDA-approved cerebrospinal fluid tests in identifying amyloid build-up and is superior in determining tau tangle levels in the brain.
APS2 blood test - This blood test is around 90% accurate at identifying Alzheimer's disease in memory clinics and primary care settings.
Lund University blood test - This blood test is up to 90% accurate at identifying Alzheimer's disease in people experiencing memory loss.
These blood tests could lead to more timely and accurate diagnosis, which could enable early intervention and better treatment. They could also make it possible to receive routine blood tests for cognitive impairment during primary care checkups, which would be ideal. However, these blood tests have not yet been approved by the FDA, and more work is needed to establish guidelines for their use in clinical practice.
Brain Scans
Computed tomography (CT): Uses X-rays to create cross-sectional images of the brain
Magnetic resonance imaging (MRI): Uses radio waves and magnets to create a detailed view of the brain
Positron emission tomography (PET): Uses a radioactive substance to detect substances in the body, including brain regions with decreased glucose metabolism
Functional Evaluations
Psychiatric evaluation
Determines if depression or another mental health condition is causing symptoms
Cognitive tests
These can include the Montreal Cognitive Assessment (MoCA), which assesses short-term memory, concentration, and understanding of time and place
Cerebrospinal fluid (CSF) tests
Also called a spinal tap, this test involves collecting CSF to look for proteins from the brain
New Treatments
TTCM2-ms
July 2024 University of Texas Medical Branch discovered a new antibody termed TTCM2 which selectively targets toxic tau buildup. This antibody was packaged in a solution to enhance its delivery though a nasal spray directly to the brain.
Targeting Tau for Destruction. TTCM2-ms slips into cells, where the antibody latches onto various forms of pathological tau. TRIM21 binds the Fc fragment of the antibody, and ubiquitinates it, targeting the entire complex to the proteasome.
Donanemab
The FDA approved this anti-amyloid medication in 2024 to treat early-stage Alzheimer's.
Lecanemab
The FDA approved this anti-amyloid medication in 2023 to treat early-stage Alzheimer's. It's the first traditionally approved treatment that addresses the underlying biology of Alzheimer's.
Blarcamesine
This drug is being tested for Alzheimer's disease and Parkinson's disease dementia. It works to stop proteins from misfolding.
Tau aggregation inhibitors and tau vaccines
These are currently being studied in clinical trials to prevent tau from forming tangles in the brain.
Aducanumab (Aduhelm)
This anti-amyloid antibody was previously approved for early Alzheimer's disease, but its manufacturer is discontinuing it.
Cholinesterase inhibitors
These medicines can help manage symptoms and slow decline. Some common cholinesterase inhibitors include Donepezil (Aricept), Galantamine, and Rivastigmine.
Stem cell therapy
AstroStem is a stem-cell-based treatment that's administered intravenously.
Pulsed Soundwave Therapy
Using gamma soundwave propagation (40 Hz) is a non-invasive brain stimulation technique that uses sound waves to help treat Alzheimer's disease.
Photobiomodulation
Red and Green Light and White Light modulated at 40 Hz has demonstrated positive effects on memory, cognition, and eye health. Inexpensive devices for each are now available.
Neurologists: These doctors specialize in the brain and nervous system and are often consulted for dementia diagnoses.
Geriatricians: These doctors specialize in the care of older adults and dementia.
Geriatric psychiatrists: These doctors are considered superspecialists for dementia diagnosis.
Behavioral neurologists: These doctors are considered superspecialists for dementia diagnosis.
Psychologists: These doctors have special training in testing to assess thinking abilities.
Neuropsychologists: These doctors can perform more comprehensive mental cognitive status tests to evaluate executive function, judgment, attention, and language.
Nutrition
As mentioned earlier, individuals with type 2 diabetes are twice as likely to develop Alzheimer’s, therefore, insulin resistance plays a significant role in the development and speed of cognitive decline associated with AD. This is especially true of non-AD age-related dementia. In this instance, glucose, the primary source of fuel for the brain, has great difficulty passing the blood brain barrier. In effect, this causes a “starvation” of the neurological tissues.
When I was in medical school, we were taught that the ONLY source of nutrition for the brain was glucose. We now know that that is not true. There is another, even more powerful, substance that can serve as food for the brain… Ketones, and they are unaffected by insulin resistance, and therefore for individuals with type 2 diabetes, ketones provide an excellent alternative for “Brain Fuel”. These can be produced by a ketogenic diet, or given directly as a Ketone ester or Ketone salt.
When discussing nutrition, it’s essential to begin with the foundation: the basic diet. Increasingly, research shows that virtually all neurodegenerative diseases are linked to insulin resistance in one form or another, a condition that typically worsens with age. As previously mentioned, insulin resistance leads to a shortage of intracellular energy in the brain because glucose cannot effectively cross the blood-brain barrier in sufficient quantities to meet the brain’s energy demands.
The first step in addressing this issue is to lower insulin resistance through dietary modifications. A good starting point is reducing sugar and refined carbohydrates. One of the most effective approaches is adopting a diet low in carbohydrates and high in healthy fats. However, making lasting dietary changes can be challenging.
Three dietary patterns that have shown promise in combating insulin resistance are the Mediterranean diet, the ketogenic diet, and the carnivore diet. Each offers unique benefits, but the underlying principle remains the same: minimizing carbohydrate intake and focusing on nutrient-dense, whole foods.
Given the context of neurodegenerative diseases, there are two primary objectives for any of the diets mentioned above. First and foremost, the goal is to lower insulin resistance throughout the body. This helps mitigate the effects of the metabolic diseases I’ve discussed previously. By reducing insulin resistance, the amount of glucose that can enter cells or cross the blood-brain barrier increases, providing the brain with the energy it needs.
In the case of Alzheimer’s or age-related dementia, this improvement in glucose uptake could have a profound impact on the brain's neurons, potentially boosting cognition, and memory. However, there's an additional strategy to consider, one that doesn’t rely solely on dietary changes: introducing exogenous ketones into the bloodstream.
Around 2010, when I was still living in the Washington DC metropolitan area, I was employed by a large nonprofit seeking to build a “green city” in nearby West Virginia. One of our objectives, aside from job oriented education for x-military, was to develop manufacturing facilities that would provide revenue sufficient to maintain the operation. Because of my position, I was very interested in anything of a medical/healthcare nature. As it turned out, I became acquainted with the chief scientist at Oxford University, Dr. Kieran Clarke, and her US counterpart, Dr. Richard Veech who was the chief of NIH metabolic lab. With approximately $10 million provided by a DARPA grant, doctors Clark and Veech developed an ingestible ketone ester earmarked for use by special forces of the US military. This substance could serve both as a “food” and as a cognitive enhancer in addition to improving physical performance.
When I learned of this project, I immediately became excited, realizing its enormous potential. Anxious to find a way to synthesize this substance on our property. Dr. Veech and I tried to accomplish that goal, which because of the economy of the time, proved to be impossible. For several years following, I continued to work with Richard searching for a manufacturing facility without success. During this time, I learned that Dr. Veech was personally treating Steven Newport with his ketone ester. His spouse, Dr. Mary Newport previously treated him with coconut and MCT oil has written a number of popular books detailing the use of Coconut and MCT oil including “What if there was a cure for Alzheimer’s and nobody knew?”. Dr. Veech shared that he was able to keep Steven functional for about another two years after the coconut oil stopped working for him, before his eventual passing.
Fast forward to the summer of 2024, when I learned that Dr. Kieran Clarke had finally partnered with a pharmaceutical company, Health Via Modern Nutrition, to synthesize the ketone ester she and Richard Veech had developed. Soon after, I discovered that the product was being marketed in the United States under the name “Ketone-IQ.” Unfortunately, this company lost its rights to produce this ketone and began producing a similar, lower grade subsitute. However, Dr. Clarke’s original British company was able to establish a manufacturing facility as deltaG Ketones in the USA. It is now the highest quality ketone ester available. It’s important to note that deltaG doesn’t require any special diet to be effective, though it’s most beneficial when used alongside coconut oil or MCT oil in a low-carb diet.
SAVE 10% on deltaG Ketones: They are by far the best ketone esters available. They were developed more than a decade ago by scientists at Oxford University and the NIH. Originally tested and developed by DARPA for special forces and elite athletes. They also dramatically improve brain health and cognitive performance.
To conclude this week's newsletter I am including a podcast by Dr. Mary Newport, the neonatologist that I mentioned above. I believe that it will provide all of you a very good overall understanding of AD and the use of Coconut, MCT, and ketone esters in the treatment of Alzheimer's. In many ways this nutritional approach provides more significant results than any drug created by big Pharma to date.
Being familiar with the condition, I sometimes wonder what active role amyloid plaque and tau protein play in the cognitive decline seen in Alzheimer's. One would have to think there is a link, but as of yet, there is no clear understanding of pathology directly involved within the neurons. Perhaps there is a coincidental non-active association, whereby the amyloid plaque serves as an antimicrobial defense mechanism to entrap and sequester pathological microbes in the brain, such as herpes simplex one.
To conclude this chapter, I am including a podcast by Dr. Mary Newport, the neonatologist that I mentioned above. I believe that it will provide all of you with a very good overall understanding of AD and the use of Coconut, MCT oil, and ketone esters in the treatment of Alzheimer's. In many ways this nutritional approach provides more significant results than any drug created by big Pharma to date. Being familiar with the condition, I sometimes wonder what active role amyloid plaque and tau protein play in the cognitive decline seen in Alzheimer's. One would have to think there is a link, yet there is no clear understanding of pathology directly involved within the neurons. Perhaps there is a coincidental non-active association, whereby the amyloid plaque serves as an antimicrobial defense mechanism to entrap and sequester pathological microbes in the brain, such as herpes simplex one.
Whatever the case, it is clear that taking a nutritional treatment approach produces verifiable improvements within human studies in cognition and function. Of equal importance, these treatments are available now without a presciption, or the involvement of medical insurance. This does not mean that interested parties should forgo expert medical consultation. However, depending on geographical and financial circumstances, there may be no choice. Furthermore, use of coconut and MCT oil, or ketone esters and salts, have few negative side-effects.
In summary, I believe that the best treatment for neurodegenerative disorders, in addition to a low-carb diet, should include an array of supplements and nutraceuticals known to stimulate and support nerve growth. Refining this further, I recommend the use of freshwater algal omega 3 supplements as opposed to fish oil, because these do not contain mercury or lead that could affect brain health. To view the embedded podcast narrated by Dr. Mary Newport simply click on the underlined title. After finishing, click on the tab at the top of the page to return to my newsletter…leave a comment and tell others about my free newsletter.
The following link is to a TED video featuring Dr. Dale Bredesen, whom I regard as one of the world’s leading research practitioners in Alzheimer’s research. Over the years, I have studied this ‘disease’ extensively in search of answers. Despite billions of dollars spent by big Pharma pursuing a singular cure—one that likely does not exist—progress has been limited. In contrast, Dr. Bredesen has identified several critical factors, primarily metabolic in nature, which make the disease treatable. If you have a friend or loved one showing signs of this devastating condition, I strongly encourage you to watch this concise, 10-minute video.
Recent News
As of February 2025, Scientific American published an article on the nature of Alzheimer’s disease, aligning with beliefs I’ve developed over the past few years. Specifically, in addition to certain genetic predispositions, Alzheimer’s appears, like many other chronic conditions, to stem primarily from metabolic insufficiencies or environmental pathogens, mycotoxins, or heavy metals that produce inflammation, leading to progressive loss of cognition.
When evaluating the increasing prevalence of chronic illnesses, a clear pattern emerges: many are closely linked to metabolic dysfunctions, often driven by poor diet and inadequate physical activity. If this is the case, it underscores the importance of addressing these factors years before symptoms manifest.
Many experts advocate for diagnosing Alzheimer’s disease (AD) based on its underlying biology rather than waiting for cognitive decline—often considered the disease's late stage. Such an approach could enable earlier diagnoses, even during asymptomatic phases like mild cognitive impairment.
This perspective aligns closely with the principles of personalized functional medicine, championed by leading Alzheimer’s researchers like Dr. Dale Bredesen. His approach involves comprehensive biomarker evaluations through extensive testing, which then inform individualized treatment plans. These plans prioritize dietary adjustments, nutritional support, and tailored exercise regimens to address each person’s unique metabolic needs.
19 mins, February 2025 - Watch this groundbreaking news featuring Dr. Dale Bredesen.
This will change everything!
Until next time, take care and stay POSITIVE…Dr. G
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