Genes and dementia
We are often asked about the genetics of dementia - whether diseases like Alzheimer's can be inherited, or passed down through families.
This page gives an overview of what genes are and how they are involved in the different diseases that cause dementia, along with information on genetic testing for dementia and current research.
What are genes?
Genes are the instructions for making living things and we inherit them from our parents. Every cell in our body contains thousands of genes. Each gene is a portion of DNA ‘code’, which holds the information our cells need to make a specific protein. Proteins make up our tissues and organs, and many have specific functions, like carrying messages between nerve cells.
What role do our genes play in dementia?
As dementia is so common, many of us will have a relative living with the condition – but this does not mean we will develop it too. Dementia is caused by diseases in the brain and in most cases our likelihood of developing dementia will depend on our age, lifestyle and the environment we live in, as well as the genes we have. For more detailed information about non-genetic risk factors for dementia, visit our risk factors and prevention page or talk to your GP.
The exact DNA code that makes up a particular gene varies naturally across the population, meaning that you might have a slightly different version of the gene to the person next to you. This is called genetic variation. Often these differences have no effect on us, but occasionally they may slightly alter our risk of diseases like cancer, diabetes and Alzheimer’s. While having a risk gene may increase the likelihood of getting dementia, it doesn’t mean a person will definitely develop it because there are many factors at play.
In rare cases, we might inherit a gene from one of our parents that doesn’t work properly. This faulty gene is called a genetic mutation and may affect how our body functions. Some mutations can have a very strong effect, and cause us to develop a disease irrespective of other risk factors. Rare forms of Alzheimer’s and some cases of frontotemporal dementia can be caused by faulty genes and passed down in families. Having one of these rare mutations makes someone almost certain to develop the disease during their lifetime.
Genes and late-onset Alzheimer’s
Late-onset Alzheimer’s affects people over the age of 65. It is the most common form of Alzheimer’s and is likely to be caused by a combination of risk factors including our age and lifestyle. Our genetic make-up may also play a part if we carry some ‘risk genes’.
To date, scientists have found versions of over twenty different genes which are associated with an altered risk of Alzheimer’s. However, having one of these versions may only have a small effect on our risk, and there is still a lot to be understood about these genes and their importance.
The most well-known Alzheimer’s risk gene is called APOE and makes a protein important for keeping our brain cells healthy. There are three different versions of this gene in the population – APOE2, APOE3 and APOE4 – and we inherit two copies, one from each parent.
People who have one copy of APOE4 (about 25% of the population) are around three times more likely to be affected by Alzheimer’s and develop the disease at a younger age. A small number of people (about 2% of the population) inherit two copies of APOE4 – one from each parent. They may be more than eight times more likely to develop Alzheimer’s. However, due to other contributing factors, they still may never develop the disease.
Is genetic testing available?
Genetic tests can be used to tell us whether we have inherited a gene linked to a particular disease and to predict whether we will develop a disease later in life. For late-onset Alzheimer’s, there is no genetic test available on the NHS. The genes discovered so far only have a relatively small effect on risk and people with them still won’t necessarily develop Alzheimer’s. Equally, people without them can still develop the disease, so such a test would not be useful.
Genes and early-onset Alzheimer’s
A small number of people with Alzheimer’s (less than 4%) develop the disease at a younger age, usually in their 50s or early 60s. For many cases of early-onset Alzheimer’s, the cause is still unclear.
A very small number of early-onset Alzheimer’s cases are caused by a faulty gene passed down in families. This can be called ‘familial’ or ‘early-onset inherited’ Alzheimer’s. It usually affects many members of the same family, typically in their 30s, 40s or 50s, but occasionally symptoms can come on at a later age. The faulty gene can only be passed down directly from an affected parent, it does not skip generations.
Three faulty genes have been linked to early-onset inherited Alzheimer’s, although others may remain to be discovered. These genes are called:
- amyloid precursor protein (APP)
- presenilin 1 (PSEN1)
- presenilin 2 (PSEN2).
These genes are involved in the production of a protein called amyloid. If the gene has a mutation and is faulty, there can be an abnormal build-up of amyloid in the brain, a characteristic feature of Alzheimer’s.
People who carry a mutation in one of these genes will develop Alzheimer’s and their children have a 50% (one in two) chance of inheriting the gene and developing the disease too. It is important to stress that faulty versions of these genes are very rare and only account for a fraction of cases of Alzheimer’s.
The Familial Alzheimer’s Disease (FAD) Support Group can help families affected by mutations in the PSEN1, PSEN2 or APP genes. More information can be found at www.fadsupportgroup.org.uk or by calling 07592 540 555.
Is genetic testing available?
Genetic testing can be offered on the NHS to someone with suspected inherited Alzheimer’s. This is a blood test, used to confirm a mutation in the PSEN1, PSEN2 or APP gene. This is known as diagnostic genetic testing and must be done at a specialist centre. A consent form must be completed before the test is given and it can take several months to get a result.
As these mutations are carried in families, it is important that a person’s next of kin, and ideally the whole family, is involved in the discussion about genetic testing. If the precise mutation affecting a person is known, it is possible for their children and siblings to be tested for the mutation too. This type of test, given to those who do not have symptoms, is called predictive genetic testing. It is only performed after a period of genetic counselling. While tests are normally considered for those over the age of 18, family members under this age can be involved in these discussions.
Genes and frontotemporal dementia
Frontotemporal dementia (FTD), originally called Pick’s disease, is a rarer form of dementia, mostly affecting people under the age of 65 years. The symptoms of FTD can be quite varied but include changes that predominantly affect behaviour or language. There are different types of FTD, and these are likely to have different causes.
Some people with FTD have a strong family history of the condition, and the disease may be passed down in these families. Several faulty genes have been found that can cause these inherited forms of FTD. Directly inherited forms of FTD are thought to account for around 10-20% of all cases of FTD. Genes that are known to cause FTD include:
- progranulin (PGRN)
- tau (MAPT)
Mutations in the tau gene can cause the tau protein to behave abnormally, forming toxic clumps that can damage brain cells. We still need to understand more about how mutations in progranulin and C9ORF72 cause the disease. The C9ORF72 gene can cause individuals to develop motor neurone disease or FTD or both conditions, and may affect members of the same family differently.
In cases of FTD that are not caused by faulty genes, the risk factors are not yet fully understood and research is ongoing. More information about frontotemporal dementia.
Is genetic testing available?
Diagnostic and predictive testing is available on the NHS for the mutations known to cause frontotemporal dementia. If there is a strong history of FTD in your immediate family, your doctor may offer to refer you for genetic testing.
Genes and vascular dementia
Vascular dementia is caused when blood flow to the brain is reduced, damaging nerve cells. This can happen as a result of a stroke or damage to blood vessels deep in the brain. The majority of cases of vascular dementia are not caused by faulty genes. We may carry genes that affect our risk of stroke, heart disease or other diseases that may contribute to vascular dementia. However, lifestyle factors such as smoking, lack of exercise, obesity, alcohol and diet can also be important.
There are rare genetic disorders which can cause vascular dementia by damaging blood vessels in the brain. One is called CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) and can be passed down through families. CADASIL only affects around 1000 people in the UK.
Genes and dementia with Lewy bodies
Dementia with Lewy bodies is caused by a build-up of abnormal proteins in the brain, and may include symptoms similar to those seen in Parkinson’s disease. Age is currently the biggest known risk factor for dementia with Lewy bodies, although research is underway to investigate whether genes may also play a role.
Dementia and Down’s Syndrome
People with Down’s syndrome have an extra copy of the APP gene which leads to the amyloid build-up associated with Alzheimer’s disease. While not everyone with Down’s syndrome will go on to develop symptoms of Alzheimer’s, the risk is much higher. The prevalence of dementia in people with Down’s syndrome increases from 2% of those aged 30–39 years, to 10% of those aged 40–49 years, 35% in people aged 50–59 years, and 55% in the age group 60–69 years.
Should I take a genetic test?
Genetic tests for mutations that cause dementia are only appropriate for a very small number of people. It depends on the disease that caused the dementia in your family, how many family members were affected and what age they developed the condition.
Deciding to take a genetic test for dementia is a big decision and requires very careful thought. Many people may not wish to know if they carry a faulty gene that causes dementia. Others may feel it would help them and their families to plan for the future.
Not all mutations that cause dementia have been identified, meaning that some families may have many affected individuals but no mutation can be found. Therefore a negative test result cannot always exclude a genetic cause of the disease.
If a test is appropriate, your doctor should be able to refer you to a genetic counsellor or geneticist. They will discuss with you the pros and cons of taking a test and any limitations the test may have. They will also tell you where the results will be kept, who they will be shared with and what the next steps would be. For people found to have a genetic mutation that causes dementia, these discussions can also cover the options available when considering starting a family.
Several months of genetic counselling are required before family members can undergo predictive genetic testing. This allows them to discuss the implications of any test result, considering a broad range of areas like finances, insurance and family planning. Predictive genetic testing is not the right decision for everyone and it is perfectly acceptable to decline testing after a period of genetic counselling.
Research into dementia genetics
Alzheimer’s Research UK has funded more than £4m of pioneering research to understand the genetic basis of dementia. Pinpointing new genes and understanding how they work provides vital clues to the cause of these diseases, taking researchers closer to new treatments.
We’re supporting researchers who are building a library of DNA samples from centres around the UK and using it to search for new genetic clues to Alzheimer’s. Find out more and visit our research projects pages to read more about other genetic studies we are funding across the UK.
We believe that dementia can only be defeated through research. Thanks to the generosity of our supporters, we hope to support many more studies into the risk factors of dementia.
This information was written in November 2014 and is due for review in November 2016. Please contact us if you would like a version with references.