Introduction to genetics
Humans have two sets of genes – one inherited from each parent – and the combination of these genes affects the characteristics we have. These genes are organised into chromosomes, with different genes located on different chromosomes.
Genes can undergo mutations where the information they carry cannot be processed correctly by the body. Many mutations occur without causing any noticeable changes to a person, but some mutations can make genes faulty and lead to diseases.
As dementia is caused by diseases of the brain, it can also be influenced by genetics. There are some non-mutated genes that can increase your likelihood of developing dementia. There are also some ways that certain genes can mutate to cause dementia. However, the vast majority of dementia cases are caused by a variety of risk factors including lifestyle features as well as risk factor genes.
One of the many genes humans have is called apolipoprotein E (APOE), which contains the instructions to make the apolipoprotein E protein. This protein’s role in the body is to bind with fats like cholesterol and transport them through the bloodstream.
The APOE gene comes in the subtypes e2, e3, and e4. Every person has two of these (one from each parent) which can be the same or a mix of two subtypes.
People who carry the APOE e4 subtype have an increased risk of developing Alzheimer’s disease earlier in life and have more of a harmful protein called amyloid-beta in their brains. Interestingly, people with APOE e2 appear to be protected against Alzheimer’s disease until later in life. Scientists aren’t sure why this is, so research is currently under way to better understand it.
The effect of each subtype increases when a person has two copies of that subtype, so people with two APOE e4 subtypes have an even higher risk of developing dementia than people with just one copy. The different subtypes of APOE are not the result of new mutations and are not faulty genes – they are simply part of the genetic differences that make us all unique.
Familial Alzheimer’s disease
Familial Alzheimer’s disease (FAD) is an extremely rare form of dementia, with just 600 families in the world known to be affected. People with FAD usually develop the condition before they reach the age of 65 – normally when they’re in their 40s or 50s.
There are three main genes that can mutate to cause FAD. They all result in the increased production of amyloid-beta, a protein which accumulates in the brains of people with Alzheimer’s disease.
These genes are:
- Presenilin 1 (PSEN1)
- Presenilin 2 (PSEN2)
- Amyloid precursor protein (APP)
Exactly how these genes are mutated varies enormously – over 230 different types of mutation have been identified.
PSEN1 mutations are the most common cause of FAD and lead to people developing dementia at an average age of 43. PSEN1 is required to make amyloid-beta, so the faulty gene leads to an overproduction of this dangerous protein, which in turn forms more protein clumps.
Mutations in the PSEN2 gene are less common than in PSEN1 and don’t result in Alzheimer’s disease developing quite as early. However, people with PSEN2 mutations live with dementia for longer and commonly experience disorientation as one of their symptoms. Like PSEN1, PSEN2 is also involved in the production of amyloid-beta.
APP mutations are also less common than PSEN1 mutations. Again, APP mutations result in people developing dementia at an earlier age than the general population due to their increased levels of amyloid-beta.
If a parent has FAD, their children will have a 50% chance of inheriting it, because they also receive 50% of their genes from their other parent. The genes that cause FAD are all dominant which means, if they are inherited, they override the non-faulty gene from the other parent. When a person inherits an FAD gene, they will go on to develop Alzheimer’s disease, as opposed to risk factor genes that only increase the chance of developing dementia.
Other types of dementia
Different types of dementia are affected by genetics to varying extents. For example, young onset dementia (under the age of 65) is more likely to be hereditary – the earlier a person develops dementia, the more likely it is due to a mutated gene.
Frontotemporal dementia (FTD) is the second most common type of dementia that affects people under the age of 65. Around 40% of people with FTD have one or more close relative with a dementia of any type, not necessarily FTD. People with a family history of FTD may have genetic FTD, which is caused by a single genetic mutation.
Familial prion diseases are a group of very rare conditions inherited from dominant faulty genes. These diseases include Creutzfeldt-Jacob disease (the human version of ‘mad cow disease’) and cause dementia very rapidly.
People with Down syndrome are much more likely to develop dementia than the general population. This is because the APP gene is located on chromosome 21, which most people with Down syndrome have three copies of.
Huntington’s disease is an inherited condition that causes dementia. Unlike in FAD, the mutated gene here is not dominant, so people whose parents have Huntington’s disease only have a 50% chance of developing the disease themselves. It is almost unheard of to develop Huntington’s disease if neither of your parents have it.
Whatever genes you have, leading a healthy lifestyle can both reduce your chances of developing dementia and slow down the rate of progression if you do have dementia. Read more about keeping your brain healthy here.