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Dietary Effects on Alzheimer's Disease Development

By Jennifer Hein

Photo credit: Pixabay

Alzheimer’s disease is the most common cause of dementia. Symptoms can include memory loss and difficulties with thinking, problem-solving and language. The symptoms usually develop slowly with age, therefore with growing life expectancy, Alzheimer’s disease is becoming more common. Although the exact cause of Alzheimer’s disease is still unknown, there are some known risk factors such as family history and lifestyle factors. There is currently no cure for Alzheimer's disease, although medication is available that can temporarily reduce some symptoms or slow down the progression of the condition in some people.

Pathological signs of Alzheimer’s disease are amyloid plaques and neurofibrillary tangles within the brain. Amyloid plaques are a sticky build up which accumulates outside nerve cells. They consist largely of a protein called beta-amyloid (Aβ), which is formed when a normal protein in the body, called amyloid, divides improperly. Neurofibrillary tangles are insoluble twisted fibres found inside the brain's cells. They consist largely of a protein called tau. [1] The tau in the tangles is found to be altered, meaning it can no longer function correctly.

Damage from oxidative stress is also found in the brains of Alzheimer’s disease sufferers. [1] Oxidative stress is an imbalance between the production of free radicals (a highly reactive and short-lived molecule which has an unpaired electron in it’s outer shell) and the ability of the body to counteract or detoxify their harmful effects.

Research has been carried out looking into epigenetic changes which are associated with the development of Alzheimer’s disease. Epigenetic changes are changes to our genes which don’t directly involve changing the DNA sequence making them up. For example, an epigenetic change could be turning a gene on or off. Genes code for proteins, so this would mean the protein that it codes for could be made when it doesn’t need to be, or not made when it should be. Epigenetic changes occur naturally and randomly, and are not inherited, as there is no change to the DNA sequence. They can, however, be influenced by environmental factors, such as diet. Epigenetic changes can occur in any cell in the body, including nerve cells. There are some known epigenetic changes in nerve cells which have been linked to the development of Alzheimer’s disease.

Photo credit: Pixabay

Clinical trials have been carried out which show following certain diets helps prevent the development of Alzheimer’s disease. One of these diets is the ‘Mediterranean’ diet. The ‘Mediterranean’ diet is largely based on vegetables, fruits, beans, whole grains, olive oil and fish. This low cholesterol diet has been implicated in the delayed development of late-onset Alzheimer’s disease. [2] It has been shown to be protective against hypertension (high blood pressure), stroke, cardiovascular disease and diabetes; conditions shown to increase cognitive decline. [3]

One of the potential mechanisms by which the diet decreases the risk of Alzheimer’s disease is by reducing oxidative stress. [4] Oxidative stress causes lipid peroxidation (the degeneration of lipids/fats). [5] Lipid peroxidation products have been found in the brain of patients with Alzheimer’s disease, [5] showing they may be involved in the development of Alzheimer’s disease.

Oxidative stress also causes hydroxymethylation of DNA. [6] This simply means a hydrogen atom is replaced with a hydroxymethyl group in a certain position in our DNA sequence. Hydroxymethylation is involved in gene regulation (turning genes on and off), so random and unnecessary hydroxymethylation can disrupt cell function. Consistent causative links between differential hydroxymethylation and Alzheimer’s disease have been shown. [7,8]

Other diets such as the ‘Dietary Approaches to Stop Hypertension’ (DASH) diet have also shown correlation with decreased risk for Alzheimer’ disease. [9] A hybrid of the ‘Mediterranean’ and ‘DASH’ diets has been reviewed, known as the ‘Mediterranean-DASH Intervention for Neurodegenerative Delay’ (MIND) dietary pattern, and has been found to provide better protection against Alzheimer’s disease than either diet on their own. [10] More research on further developing these diets could be undertaken to potentially find a more effective diet in the prevention of Alzheimer’s disease.

The ‘Mediterranean’, ‘DASH’ and ‘MIND’ diets all involve eating a high proportion of foods which have a high flavonoid content. Flavonoids are famous for their antioxidant and anti-inflammatory health benefits. Antioxidants help to reduce oxidative stress. Antioxidants are found in a variety of fruits and vegetables, especially apples, bananas, blueberries, tomatoes and peppers. Flavonoids have also been shown to interact with some signalling pathways, which inhibit nerve cell death and provide neuroprotective effects. [11,12] Flavonoids increase the expression of neuroprotective and neuromodulatory proteins, as well as increasing the number and strength of synapses (connections between nerve cells) in the brain. [11,12]

Photo credit: Pixabay

Along with their antioxidant effects, flavonoids have been suggested to directly inhibit BACE-1 activity. [13] BACE-1 is the rate-limiting enzyme responsible for A%beta; production, the protein which forms the amyloid plaques which are found in high concentration in the brains of Alzheimer’s disease sufferers. BACE-1 activity is therefore considered to be a prime target in preventing Alzheimer’s disease. [13]

Vitamin B12 and folate (found in high concentration in liver, dried beans, lentils, wholegrain breads etc.) also influences BACE-1 activity, through DNA methylation. [14] DNA methylation is similar to DNA hydroxymethylation, but instead of a hydroxymethyl group being added to a base, a methyl group is added. A deficiency in vitamin B12 and folate results in insufficient DNA methylation. [14] A lack of methylation to a certain binding site, called SP1, leads to an increase in BACE-1 expression. This therefore results in elevated A%beta; production. However, mixed results have been shown from clinical trials as to whether or not vitamin B12 and folate have a significant effect on the development of Alzheimer’s disease.

Current research has given us a comprehensive overview of the impact of diet on Alzheimer’s disease development. However, more long-term clinical trials need to be carried out to prove or disprove current suggestions. Overall, diet seems to have a large impact on Alzheimer’s disease pathogenesis, although the mechanisms aren’t always known or understood.

Useful links and resources

Alzheimer’s society ‘What is Alzheimer’s disease?’ http://www.alzheimers.org.uk/site/scripts/documents_info.php?documentID=100

NHS ‘Alzheimer’s disease’ http://www.nhs.uk/conditions/Alzheimers-disease/Pages/Introduction.aspx

NHS ‘What is a Mediterranean diet?’ http://www.nhs.uk/Livewell/Goodfood/Pages/what-is-a-Mediterranean-diet.aspx


References

  1. Alzheimer's Disease. http://www.alz.org/professionals_and_researchers_13519.asp [accessed 18 March 2015]
  2. C. Lythgoe et al., Neurobiol. Aging, 2015, 36, 547e1-3
  3. C. C. Tangney, Current nutrition reports, 2014, 3, 51-61
  4. H. F. Lopes HF et al., Hypertension, 2003, 41, 422-430
  5. G. Di Paolo and T.-W. Kim, Nature Reviews Neuroscience, 2011, 12, 284-296
  6. M. Tellez-Plaza et al., Environmental Health Perspectives, 2014, 122, 946-954
  7. K. Lunnon et al., Nature Neuroscience 2014, 17, 1164-1170
  8. P. L. De Jager et al., Nature Neuroscience, 2014, 17, 1156-1163
  9. H. Wengreen et al., The American Journal of Clinical Nutrition, 2013, 98, 1263-1271
  10. M. C. Morris et al., Alzheimer's & Dementia: The Journal of the Alzheimer's Association, 2015, 11, 1007-1014
  11. J. P. E. Spencer JPE, Proceedings of the Nutrition Society, 2010, 69, 244-260
  12. R. J. Williams and J. P. E. Spencer, Free Radical Biology and Medicine, 2012, 52, 35-45
  13. Paris D et al., Bioinformation, 2011, 6, 229-236
  14. D. K. Lahiri and B. Maloney, Experimental Gerontology, 2010, 45, 291-296

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