How our genes tell the story of our future


According to the World Heath Organisation (WHO), there are an estimated 18 million people worldwide with Alzheimer’s disease. This figure is projected to nearly double by 2025 to 34 million. Much of this increase will be in the developing countries, and will be due to the ageing population. The theme for World Alzheimer’s Day, due to fall on September 21st, is ‘Dementia. It’s time for action!’ The focus this year centres on raising awareness and improving service provision for people with dementia and their carers.

There has been much attention in the media and press recently regarding the development of dementia in later life and the methods needed to reduce the incidence. Having detailed information on an individual’s predisposition status to the disease would certainly allow that person to make significant changes, both in diet and lifestyle, to help reduce this risk. Lipoproteins, such as high-density lipoprotein (HDL) and low-density lipoprotein (LDL), are combinations of lipids (fat) and protein that function to transport fat around via the blood, a function that is generally associated with cholesterol, and therefore cardiovascular health. However, approximately 1 in 7 people carry a gene that causes their body to produce a particular lipoprotein known as ApoE4, known to play a significant role in the development of Alzheimer’s disease. People who inherit the ApoE4 gene from one parent are three times more likely than average to develop Alzheimer’s, with those inheriting the gene from both parents having a tenfold risk of developing the disease (Donix et al, 2010).

Whilst there is a genetic test that can be performed to evaluate if an individual is a carrier of the ApoE4 genotype, it is performed mostly in those cases where an individual has consistently high levels of cholesterol and triglyceride that do not respond to statin therapy. This is because another quite severe downside to being a carrier of the ApoE4 version of the gene is that it also carries an increased risk of developing atherosclerosis, a condition in which fatty deposits build up in the arteries, causing restrictive blood flow that, if severe enough, could lead to heart attack or stroke. The risk of developing atherosclerosis can usually be reduced by the use of statins, or alternatively the consumption of omega-3 fish oils, which act to lower LDL or ‘bad cholesterol’ and increase HDL or ‘good cholesterol’. In individuals with the ApoE4 genotype, a common observation is an increase in total cholesterol and LDL in response to taking high dose fish oil, and this pro-atherogenic shift is likely, in part, to negate the cardio-protective action of fish oil seen in these individuals. A recent study has, however, shown that this effect is only evident in response to DHA oils. Generally, fish oils contain two long chain omega-3 fatty acids, EPA and DHA. Fish oil has for many years been used successfully to treat cases where there is high cholesterol and/or high levels of triglycerides, which are themselves known to increase the risk of cardiovascular disease (CVD). Given the positive association between fish oil and CVD, there has been much interest focusing on the individual role each fatty acid plays in modulating various risk factors for CVD. In a study published earlier this year in the journal Atherosclerosis, individuals with the ApoE4 genotype who supplemented with DHA, showed a rise in their cholesterol levels; in contrast, however, when they supplemented with EPA, there was no increase in cholesterol levels (Olano-Martin et al, 2010), implying that EPA oils may be a more suitable therapy for regulating both triglyceride and cholesterol, certainly in those individuals at an increased risk of developing atherosclerosis.

The good news is that EPA not only has a major cardio-protective role, but also has a protective role within the brain, by preventing the formation of beta amyloid damage caused in part by ApoE4. ApoE4 normally attaches itself to a particular receptor on the surface of brain cells, which then adheres to a protein called amyloid precursor protein (APP), which then migrates inside the cell. Once inside, APP is fragmented into beta amyloid pieces by enzymes called proteases; high levels of beta amyloid are associated with reduced levels of the neuro- transmitting chemical messenger acetylcholine, essential for memory and learning and progressively destroyed in Alzheimer’s patients. By interfering with protease enzymes, EPA prevents the fragmentation of the amyloid precursor protein, thus preventing the production of beta amyloid.

Given that EPA fish oil can not only reduce the risk of both atherosclerosis and dementia through the involvement of ApoE4, how long will it be before individual nutritional regimes, as a result of genetic screening, become the ‘norm’ within our health service, as a means to reduce the incidence of these conditions as we age? The concept of using genotyping to determine an individual’s personal risk of developing a variety of conditions and/or diseases based on their genetic make-up is not new. Certainly, knowing an individual’s particular risk of developing specific disease could, in future, result in personalised nutrition as a preventative method against developing such disease.

References
Donix M, Burggren AC, Suthana NA, Siddarth P, Ekstrom AD, Krupa AK, Jones M, Rao A, Martin-Harris L, Ercoli LM, Miller KJ, Small GW, Bookheimer SY. (2010) Longitudinal changes in medial temporal cortical thickness in normal subjects with the APOE-4 polymorphism. Neuroimage. 53:37-43.

Olano-Martin E, Anil E, Caslake MJ, Packard CJ, Bedford D, Stewart G, Peiris D, Williams CM, Minihane AM. (2010) Contribution of apolipoprotein E genotype and docosahexaenoic acid to the LDL-cholesterol response to fish oil. Atherosclerosis. 209:104-10.

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