Running head: MITOCHONDRIA AND ALZHEIMER’S DISEASE 1

Mitochondria and Alzheimer’s Disease

Melissa Chandler

Salt Lake Community College

MITOCHONDRIA AND ALZHEIMER’S DISEASE 2

Abstract

Alzheimer’s disease is a debilitating progressive neurodegenerative disorder that is clinically

characterized by the progressive loss or damage of cholinergic neurons in the brain. This leads

to the onset of behavior, motor, and cognitive impairments that may become severe. Poor diets,

genetics, and lack of active lifestyles are identified as key factors that put individuals at

heightened risk. There is no known cure or effective treatment for Alzheimer’s disease and

many of the therapies currently in practice today are yielding little results in animal trials. The

therapies provide symptomatic relief only, and while the molecular basis underlying the

multifactorial neurodegenerative disorder challenges the scientific community, mitochondria

dysfunction and glucose levels play a critical role in the pathogenesis of this disease.

Keywords: Mitochondria, MIND, Ketogenic, Apolipoprotein, APOE ε4, Glucose

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Factors and Alzheimers Disease

For years now doctors and nutritionists have adopted the ketogenic and MIND diet to

help slow down the occupancy of seizures and other brain diseases that are affected by improper

glucose levels in the brain. My argument is that foods that are higher in good fat can help slow

down and reduce symptoms of Alzheimer’s disease by helping improve mitochondrion function.

Causes of Alzheimers Disease

According to the U.S. Department of Health & Human Services National Institute on

Aging (NIH), there have been no breakthroughs in finding causation behind Alzheimer’s disease.

There are several factors that have been clinically proven to help attribute to the underlying

symptoms of Alzheimers. Per NIH, poor nutrition and low physical fitness amongst other factors

listed as contributing to increased risk for pathogenicity of the disease. (Alzheimers, 2016).

Mitochondria deficiencies and lack of glucose production is a key problem found in Alzheimers

patients. These deficiencies make it hard for the brain to function properly because it cannot

complete vital functions that rely on the energy source glucose. Genetics is also another

contributing factor. Apolipoprotein E (APOE) gene, also referred to as the APOE ε4 allele,

plays an important role in Alzheimer’s. The allele APOE ε4 is responsible for breaking down

fats in the body.

Ketogenic and Fasting – High-Fat Diets

Ketogenic is a diet based on similar principles shared by the MIND diet that involves

fasting and eating foods mostly dense in good fats every twelve hours. In chapter three of our

course book states “during fat catabolism triglycerides are first broken down to glycerol and fatty

acids. The glycerol can be converted to glucose in the liver”. (Mader, Windelspecht, 2016, page

73). This glucose is then broken down further to create pyruvate acid during glycolysis and two
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adenosine triphosphate (ATP). Glycolysis happened outside of the mitochondria however it is

the first step of cellular respiration. From glycolysis, the preparatory stage converts pyruvate

acid to acetyl CoA that is used in the citric acid cycle (produces two additional ATP). The final

step of cellular respiration is electron transport chain and oxidative phosphorylation and this

process yields a large quantity of ATP, around 34 total. (Mader, Windelspecht, 2016, page 72).

The ATP created by the mitochondria in the brain is directly responsible for feeding vital brain

functions and processes including production of different essential enzymes.

The ketogenic diet per the perfect keto website discusses the correlations between blood

glucose levels and Alzheimer’s disease, even labeling Alzheimer’s as stage three diabetes.

(Gustin, 2018). The diet concentrates on lowering glycemic index by “replacing foods with

wholesome fats like low carb nuts, avocados, grass-fed meats, and high-quality oils”. (Gustin,

2018). There was evidence with this diet however that indicates individuals who do not “have

the apolipoprotein E (APOE) gene or APOE ε4 allele” (Gustin, 2018) might not find the diet

useful. Apolipoprotein E and APOE ε4 are genetically passed from family members and it puts

the individual at higher risk but does not guarantee pathological progression of the disease.

Apolipoprotein E is a protein involved in metabolizing fats in the body, so adding fat would not

help in this case, in fact, individuals who lack this gene may also suffer from cardiovascular

disease as well.

Scientists in London conducted a three-month clinical test and found that “a diet

comprised of 70% fat improved cognition in Alzheimer’s disease patients.” (Sullivan, 2018).

This further supports the claims that perfect keto diet makes and my argument. The University

of Kansas conducted their own pilot study on Alzheimer’s patients who followed the ketogenic
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diet and found an average improvement by four points on one of the most important cognitive

assessments, the Alzheimer’s disease assessment scale. (Sullivan, 2018).

All of the evidence supports my argument that diets high in wholesome fats and omega

fats can decrease and in some cases reverse additional damage during the diseases pathological

process. Individuals who may consider trying this approach to treating progressive brain

disorders should consult with their doctors and dietitians prior to starting a high-fat diet. For

one, it can interfere or exasperate a health condition especially those with an inability to

efficiently break down fat or those who suffer from cardiovascular disease. There are other

options like the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet.

This diet is a combination of lower sodium, plant-focused Dash diet, and the heart-healthy

Mediterranean diet. (Sullivan, 2018). The diet is focused on lower fat intakes (33%) compared

to the keto diet (70%). Another consideration is that too much glucose can be just as harmful as

too little. A study conducted on animals by scientists at the University of Montreal and Boston

College linked excessive glucose consumption to memory and cognitive deficiencies. (Edwards,

2016).

Mitochondria Dysfunction

Mitochondria dysfunctions is another factor that is contributing to a higher risk for

Alzheimer’s disease. Many studies are currently underway that target mitochondrial dysfunction

because it remains a molecular basis that underlies this multifactorial neurodegenerative disorder.

(Onyango, Dennis, Khan, 2016). However, “while mitochondria therapeutic strategies show

promise, there has been little progress in clinical trials thus far”. (Onyango, Dennis, Khan, 2016).

In fact, many of these therapy trials have not made it past animal testing because they are not

yielding great results. Most of the therapies currently available deal with correcting a deficiency
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on a molecular level, within the mitochondria itself. There are several phases of both mitosis and

cell cycle were errors can occur causing replication of cells with dysfunctional mitochondria.

Other therapies such as diet and exercise have been studied and the results show an

overall improvement in symptoms of Alzheimer’s. Exercise is vital in additional mitochondrial

production. The exercise that is recommended varies depending on who you talk to but most

will agree that high-intensity training is ideal. High-intensity workouts are becoming the new

rage and involve either vigorously biking or walking for 20 minutes 4 times a week or weight

training. The consensus is, however, “exercise training alone or combined with a caloric

restrictive diet may represent an efficient strategy to delay mitochondrial aging and age-related

dysfunction by stimulating mitochondrial biogenesis and oxidative capacity.” (Onyango, Dennis,

Khan, 2016). A study published on March 7 in Cell Metabolism found “exercise — an in

particular high-intensity interval training in aerobic exercises such as biking and walking —

caused cells to make more proteins for their energy-producing mitochondria and their protein-

building ribosomes, effectively stopping aging at the cellular level”. (CellPress, 2017).
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Conclusion

The causes of Alzheimer’s disease is still widely unknown, however many factors

contribute to increased risk of developing symptoms that result in the disease. Medicine and

other therapies are used in treating this progressive disease, however, diet and moderate physical

exercise have been proven to help slow down if not stop the pathology of the disease in people

who do not have the apolipoprotein gene or the APOE ε4 allele.

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References

Alzheimer's Disease Fact Sheet. (2016, August 17). Retrieved November 15, 2018, from

https://www.nia.nih.gov/health/alzheimers-disease-fact-sheet#diagnose

Cell Press. (2017, March 7). How exercise -- interval training in particular -- helps your

mitochondria stave off old age. ScienceDaily. Retrieved November 29, 2018 from

www.sciencedaily.com/releases/2017/03/170307155214.htm

Edwards, S. (2016, March). Sugar and the Brain. Retrieved November 16, 2018, from

http://neuro.hms.harvard.edu/harvard-mahoney-neuroscience-institute/brain-newsletter/and-

brain-series/sugar-and-brain

Gustin, A., DC, MS. (2018, August 17). Ketosis for Alzheimer's Disease. Retrieved

November 17, 2018, from https://perfectketo.com/ketosis-for-alzheimers-disease/

Mader, S. S., & Windelspecht, M. (2016). Human biology (Custom Editionfor Salt Lake

Coummunity College ed.). New York, NY: McGraw-Hill.

Onyango, I. G., Dennis, J., & Khan, S. M. (2016). Mitochondrial Dysfunction in

Alzheimer's Disease and the Rationale for Bioenergetics Based Therapies. Aging and disease,

7(2), 201-14. doi:10.14336/AD.2015.1007

Sullivan, M. G., & Clinical Neurology News. (2018, April 16). Fueling the Alzheimer's

brain with fat. Retrieved November 18, 2018, from

https://www.mdedge.com/clinicalneurologynews/article/145220/alzheimers-cognition/fueling-

alzheimers-brain-fat