Genetics and the Development of Alzheimer's Disease
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You opened your eyes, and as your eyes adjusts to the darkness, you realised that you are in room that you do not recognise. Everything looked foreign, you don’t recognise the people in the picture frame hung on walls, the bedsheet feel rough and unfamiliar, and you start to feel a growing fear gnawing at the edges of your heart.
Have you ever wondered what it would feel like to have Alzheimer’s disease? Have you ever been in a classroom, when the teacher called out to you to answer a question, but you don’t have the answer to that question? Do you remember that feeling of shame and embarrassment? Now imagine feeling like that every single day, except that your school classroom is replaced by the huge classroom of the world around you, where you are constantly frustrated and embarrassed for forgetting things and people.
What is Alzheimer’s disease?
Did you know that our brains are active 24-7, filled with a series of neurons firing away rapidly at all times, even when you are sleeping? These neurons are supported by a complex ecosystem of proteins, ions and chemicals that works together. However these carefully balanced ecosystem can be disrupted, causing the neurons to deteriorate progressively and eventually leading to diseases like Alzheimer’s.
Alzheimer’s disease is a progressive and irreversible form of brain disease, and it is characterized by gradual loss of memory and cognitive skills. As with many other conditions, the development of Alzheimer’s disease is influenced by a combination of genetics, age, lifestyle, environmental and medical factors. Most people diagnosed with Alzheimer’s disease only starts seeing the symptoms of the disease in their mid-60’s or later.
However, let’s look at how your genes play a role in your risk of developing Alzheimer’s disease.
Alzheimer’s disease and the associate genes
In the vast majority of people, any genetic risk of Alzheimer’s disease, whether it’s increased or decreased risk, is linked to variations in a large number of susceptibility genes that they have. There are many pathways linked to Alzheimer’s disease, which are inflammatory response, lipid metabolism and endocytosis.
Figure 1: Major pathways involved in Alzheimer’s disease and the associated genes, obtained from here.
One of the first genes discovered to be associated to Alzheimer’s disease is the APOE gene, which codes for APOE protein, the major cholesterol carrier in the brain. There are 3 major variants (also known as alleles) of APOE gene:
- APOE ε2
This is the rarest form of APOE, and may reduce the risk of developing Alzheimer’s disease.
- APOE ε3
This is the most common allele and does not seem to increase/decrease the risk of developing Alzheimer’s disease.
- APOE ε4
This allele is present in approximately 10-15% of people, it is associated with an increase risk of developing Alzheimer’s and associated with earlier age of disease onset. A person can have 0, 1 or 2 APOE ε4 alleles, and the risk of developing Alzheimer’s disease increases with the number of APOE ε4 alleles.
Even though APOE ε4 increases a person’s risk of developing Alzheimer’s disease, having the APOE ε4 allele DOES NOT mean that a person will definitely develop Alzheimer’s disease. There are people with APOE ε4 alleles and never develop Alzheimer’s disease, while there are people diagnosed with Alzheimer’s disease who do not have APOE ε4 alleles.
Scientists have also discovered a number of other genes that are associated with the risk of developing Alzheimer’s disease, which we will not go into today. If you are interested, check out this table to learn more.
What can I do with when I learn about my genetic risks?
It’s important for us to remember that the development of Alzheimer’s disease is multifactorial, and it includes other factors such as lifestyle and environmental factors.
Knowing is better than not knowing. However, do know that having this knowledge can potentially empower people to make more informed decisions, and that can be a powerful tool to have.
Even though you can’t change your genetic risk factors, it is just one of the many risk factors. There are other risk factors that you have control over, for example your lifestyle, diet and other factors. With knowledge over your genetic risk, it can be an important motivator to push you towards a healthy lifestyle and other interventions.
1. National Institute of Aging. (2015). Alzheimer’s Disease Genetics Fact Sheet [Online]. Available at: https://www.nia.nih.gov/health/alzheimers-disease-genetics-fact-sheet [Accessed 20 Dec 2018]
2. Genetics Home Reference. (2018). Alzheimer disease [Online]. Available at: https://ghr.nlm.nih.gov/condition/alzheimer-disease [Accessed 20 Dec 2018].
3. Clin Interv Aging. Genes associated with Alzheimer’s disease: an overview and current status. 2016; 11: 665–681. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876682/ [Accessed 20 Dec 2018].
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