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The Genetics of Alzheimer’s Disease

· health,vitamins,alzheimers disease,longevity

In the National Geographic series, Limitless, Chris Hemsworth goes on a journey of extreme proportions to test the limits of the human body. He walks along a plank off a high rise, goes on a fast for 4 days, surfs in near minus temperatures in the Norwegian arctic and climbs a rope hanging off a ski lift in the middle of a forest. However, what is gradually revealed in the series is that his grandfather had been suffering from Alzheimer’s for some time and after a genetic screening, Mr. Hemsworth found that he carried two copies of the APOE4 gene which, according to experts, puts him at a much greater risk of developing Alzheimer’s.

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Chris Hemsworth surfing in near freezing temperatures in the Norwegian Arctic, from the series Limitless, still image, National Geographic 2022.

What is APOE4?

APOE4 gene is a variant of a gene that is responsible for the metabolism and transport of apolipoprotein E. The population that most commonly has the APOE4 variant is West Africa. This gene allows faster metabolism of cholesterol, hence people who possess this variant may have physiques that are lean, muscular and lanky despite consuming a large amount of fatty foods. However, due to this enhanced metabolism of cholesterol, people with the APOE4 variant also may have higher levels of lipid cholesterol in their bodies, and this high cholesterol level may affect synaptic functions in the brain in which may develop into neurodegenerative conditions such as Alzheimer’s, amyotrophic lateral sclerosis, and Parkinson’s disease.

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The population with a high number of people with the APOE4 gene variant is in West Africa, but there is little incidence of Alzheimer's disease in the region.

However, we must consider that APOE4 is not indicative of future Alzheimer’s as the variant is widely present in West African populations with very little trace of the disease. In fact, the APOE4 variant may be ideal for people who are athletes and highly physically active, as the enhanced cholesterol metabolism also leads to enhanced strength and ability to recover quickly from injuries and disease.

Lifestyle vs. Genetics

We have to consider many lifestyle factors that often lead to neurodegenerative conditions and often what affects our genes’ ability to switch on and off and work optimally are mainly due to one’s diet. It has been found that people who have Alzheimer’s and other forms of dementia are often deficient in vitamin K2.

Since the 1970s, the western diet has consisted of more meat and fatty foods than in previous eras, where a high fat, high protein consumption has led to the overwhelming health conditions in which many critics have said that the western world is in an obesity epidemic. Despite that many people, including doctors, often praise intermittent fasting and ketogenic diets as solutions for our ever growing high protein, high fat diets, we have to consider that the populations in the world such as Japan and South Korea, which have the longest lifespan and longevity often adhere to the opposite- a high carb, low protein, low fat diet.

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South Korea, a nation that has one of the healthiest populations in the world, with the highest longevity, has a diet that mainly consists of carbohydrates from rice, vegetables and fruits with little protein in their daily consumption. The United States, in which a high protein, high fat diet is consumed daily by the population is ranked one of the highest nations for incidence in Alzheimer's disease and ranks 8 in the world. In comparison, South Korea ranks as one of the lowest nations for Alzheimer's disease and ranks 154.

In genetic screening, experts often reveal a systemic reporting of conditions based on certain genes amongst the population, but we have to remember that lifestyle choices are vastly more important when determining the future incidence of disease.

Substances and Foods to Avoid for APOE4 carriers

- Foods high in phosphorus– such as cow’s milk, dairy, sodas/fizzy drinks with artificial sweeteners

- Foods high in protein- such as protein shakes and large consumption of meat

- Foods high in fat and cholesterol- such as red meat, bacon and other processed meats

- Drugs- such as statins, benzodiazepines, GABA agonists, anabolic steroids

Instead of a high fat, high protein diet, the optimal diet for APOE4 carriers, or even for the general population at large, should be high carb, low protein and low fat. Keto diets, high protein diets or fasting should be avoided. For physically active people such as Mr. Hemsworth, a 4 day fasting period seems extreme and rather unnecessary. Although the medical expert in the series, Dr. Peter Attia, describes fasting as a way to enhance ketone production and to stimulate cells towards autophagy, another way to achieve this without fasting is doing what athletes call a “niacin flush”.

A niacin flush is taking a high amount of vitamin B3 for a short period which results in red flushing of the skin as the vessels expand and essentially flushes out toxins and has a cholesterol lowering effect. Vitamin B3 is also a necessary component of genetic repair and induces autophagy (ie, the recycling of cells).

One of the dangers of fasting for prolonged periods, especially for physically active people, is that it puts great stress on cardiovascular functions, in addition to depleting taurine from muscles which may result in muscle degeneration. Certainly fasting has been shown to be beneficial for people who suffer from cancer or those who are obese, but for people who are physically active and athletic, fasting may have more negative effects than positive as physically active people need a constant source of nutrition and fuel as opposed to the much lower requirements of sedentary people.

For men like Mr. Hemsworth, who trains multiple hours a day and is constantly on the move, fasting would not have much benefit at all and may, in fact, cause injury to his heart and cardiovascular functions in addition to damaging his muscles.

Because APOE4 carriers are also at risk for cardiovascular disease, a high protein diet should be avoided. High protein diets are often associated with negative cardiovascular effects and it has been shown that too much protein is not a good thing despite our consumerist marketing agencies touting many protein powders for bodybuilders, it often has detrimental effects. 

Drugs such as statins should be avoided, mainly due to its effect on cholesterol metabolism and also other drugs that negatively affect brain function such as benzodiazepines, GABA agonists such as Ambien, and anabolic steroids.

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Chris Hemsworth on the set of Thor from the series Limitless, still image, National Geographic, 2022.

Many Hollywood actors often take anabolic steroids in order to prepare for their roles in action movies, however, steroids also affect cholesterol levels that may lead to cognitive decline, in addition, steroids have been shown to accelerate ageing and have overall negative health impacts.

Instead of anabolic steroids, taurine may be utilised to enhance muscle strength. Taurine is an amino acid and neurotransmitter that is necessary for the development of muscles, as well as having positive effects on vision, cardiovascular health as well as necessary for cell proliferation and collagenogenesis (ie, production of collagen).

Although some controversy has been associated with taurine which had been added to energy drinks with a high amount of caffeine, the negative effects of energy drinks are most likely isolated to the high amount of caffeine, and not due to the taurine. It has been said that people in Okinawa have a diet high in taurine, which is often associated with their longevity.

Beneficial Supplements to Prevent Alzheimer’s

- Vitamin K2

- Vitamin B3 (niacin)

- Taurine

- Coenzyme q10

All in all, APOE4 variant carriers have enhanced cholesterol metabolism, which is ideal for athletes and physically active people, but for those who are inactive, and eat a high fat, high protein diet, this may have negative effects which may eventually lead to neurodegenerative conditions such as Alzhemier’s.

However, for people who just can’t give up their medium-rare steaks and daily rashes of bacon, supplements may be beneficial to enhance the body’s own ability to induce self-healing.

Vitamin K2 may be the most important supplement for people for the prevention of Alzheimer’s and other neurodegenerative diseases. K2, in particular the MK-7 variety present in fermented foods, has the ability to enhance immunity as well as to prevent the calcification of blood vessels. It has been shown that K2 has the ability to redirect calcium into bones to prevent calcification of blood vessels, to break down hardened vessels as well as enhance cognitive functions. K2’s inhibition of arterial stiffening and arterial calcification lowers the risk of vascular damage, which is key in preventing cardiovascular conditions in which a stroke may lead to other neurodegenerative conditions such as dementia. Researchers have also noted the role of K2 in the prevention and treatment of Alzheimer’s.

As mentioned previously, niacin also induces autophagy, a process in which cells “eat” old cells for recycling and niacin is essential for DNA repair.

Taurine and Coenzyme q10 are important for cardiovascular health, and taurine has positive effects on muscle enhancement, which could replace the need to take anabolic steroids. Although carriers of the APOE4 gene may predispose them to develop Alzheimer's and cardiovascular disease when consuming a western diet that is high in protein and fat with low dietary K2 and B3, we have to remember that carriers of this gene in West Africa often do not suffer from the same neurodegenerative conditions as people in Western nations.

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Chris Hemsworth walking down a plank on top off a high rise, thousands of feet from the ground with only a single cable holding him for support. From the series Limitless, still image, National Geographic, 2022.

Although Chris Hemsworth’s Limitless series shows us one side of the APOE4 variant, we have to also remember that its specific enhanced ability to metabolise cholesterol is probably one of many collective factors which also gives Mr. Hemsworth his athletic prowess and lean, muscular physique.



Disclaimer: This article is not intended as medical advice and is for educational purposes only in order to stimulate conversation and dialogue regarding everyday and controversial topics in order to gain a deeper understanding of our world.