Can genes cause dementia?

Around 1 in 4 people aged 55 years and over has a close birth relative with dementia. Find out what part genes play in dementia and how genetics can affect the risk of developing the condition.

It is well known that children can take after their parents – for example, in the way they look. This is partly because many of the key characteristics of a person are passed down from parents to children in their genes.

What are genes?

Genes are made from a chemical called DNA. They contain information that is needed to make proteins, which the body is built from. Humans have over 20,000 different genes. Most often, a person has two copies of each gene – one inherited from each parent.

What is a gene variant?

The same gene can differ between individuals – these are known as ‘gene variants’. These can help to explain why people are different to each other – for instance, why one person has blue eyes and another person has brown eyes.

If a gene variant increases a person's risk of developing a disease, it is known as a 'risk variant' for that disease.

How can genes cause disease?

Genes often play a role in the development of diseases. This can happen in two main ways.

Single-gene diseases

Sometimes, a gene changes and this causes a disease. This is known as a single-gene disease because it is caused by a change in just one gene. Single-gene diseases are often serious, but they are rare.

It is possible to directly inherit a single-gene disease. This means that if a child inherits the same changed gene that a parent has, they are very likely – in some cases almost certain – to develop the same disease.

Complex or multiple-gene diseases

Complex diseases are less straightforward. They develop through the interaction between several different factors. These are known as ‘risk factors’ for that disease. They include:

  • the person’s environment or lifestyle – for example, their diet and whether they smoke or not
  • multiple gene variants – known as ‘risk variants’ because they increase the person’s risk of developing the disease.

It isn’t possible to inherit a complex disease in the same way as a single-gene disease. This is because complex diseases are caused by multiple factors acting together.

However, a person with a family history of a complex disease will often have an increased chance of developing it. This is because they are likely to share risk factors with other birth relatives. Despite this increased chance, the person still might never develop the disease.

How can genes cause dementia?

Most often, dementia is caused by a complex disease in which genes are only one factor. When this happens, the dementia develops as a result of many different factors. In these cases, genes do not directly cause it to develop.

It is not possible to directly inherit dementia when it is caused by a complex disease.

Dementia caused by a complex disease

Nearly all cases of dementia are the result of a complex disease. In these cases, genes may increase the risk of developing dementia, but they don’t cause it directly.

What causes complex disease dementias?

When dementia is the result of a complex disease, it is likely to be caused by a combination of risk factors. These include:

  • non-genetic factors – for example, members of the same family may all smoke or have an unhealthy diet, which are both risk factors for dementia. 
  • genetic factors – a person may inherit the same dementia risk variants as other members of their family. This could include variants in genes such as APOE.

These factors are often shared by members of the same family. This is why many people have some family history of dementia – for example, they may have a parent who developed dementia in their 90s and a brother who developed dementia in his 70s. This is not the same as ‘familial dementia’.

Is it possible to directly inherit dementia when it's caused by a complex disease?

No. People who are related to each other by birth are more likely to have the same risk variants as each other. However, risk variants for dementia do not directly cause dementia (like a single-gene change does). This means that it’s not possible to directly inherit dementia through risk variants.

However, a person who has dementia risk variants is at higher risk of developing dementia than someone who does not have risk variants. Despite this higher risk, they still might not develop dementia.

Which gene variants increase the risk of dementia?

The most well-known risk variants for dementia are for Alzheimer’s disease. These are in the apolipoprotein E gene – more commonly known as the ‘APOE’ gene.

Over 20 other genetic variants have also been identified as risk variants for Alzheimer’s disease. However, most of these variants only increase a person’s risk of developing Alzheimer’s very slightly.

How does the APOE gene increase the risk of dementia?

This gene has three common variants: APOE2, APOE3 and APOE4. Of these three, APOE4 is the one that most increases a person’s risk of developing dementia.

A person can have no copies, one copy or two copies of APOE4 – depending on what they inherited from their parents. The more copies of APOE4 that a person has (none, one or two), the higher the risk is of them developing Alzheimer’s disease.

APOE variants are also risk factors for dementia with Lewy bodies (DLB) and vascular dementia.

Will a person with APOE variants definitely develop dementia?

No. APOE variants do not directly cause dementia. This means that:

  • Some people have two copies of APOE4 but never develop dementia.
  • Many people do develop dementia even though they have no copies of APOE4.

This is why testing for gene variants like APOE is not helpful in telling whether or not someone will develop dementia.

Can a person with dementia risk variants reduce their chances of developing dementia?

Yes. People with risk variants for dementia can still reduce their chances of developing the condition by leading a healthy lifestyle. For example, if the person eats a well-balanced diet, is physically active, doesn’t smoke and doesn’t drink too much alcohol, they will reduce their overall risk of developing dementia.

In some rare cases, dementia is caused directly by a single-gene disease.

In these cases, the dementia can be inherited from parent to child.

Dementia caused by a single-gene disease

Of the four most common types of dementia, frontotemporal dementia (FTD) is most likely to be caused by a single-gene change. 

Is dementia different when it's caused by a single-gene change?

Yes, it can be different in some ways.

  • It often develops earlier in life. For example, an affected person might get dementia in their 40s or 50s rather than in their 70s or above. This is known as ‘young-onset’ dementia
  • It tends to run strongly in families, with several close relatives who develop the same type of dementia. For example, a person with a single-gene dementia may have a grandparent, a parent and a brother who all had frontotemporal dementia (FTD). This is why dementia caused by a single-gene disease is sometimes known as ‘familial dementia’.

Can single-gene dementias be inherited directly?

Yes. If a single-gene dementia is present in a family, it is quite likely that a person from that family will develop dementia:

  • If one of the parents carries the changed gene, each child has a 1 in 2 chance of inheriting it.
  • If one of the children carries the changed gene, any brothers or sisters they have has a 1 in 2 chance of carrying it as well.

For these families, counselling and genetic testing may be helpful.

Rare types of dementia caused by a single-gene change

There are some rarer types of dementia that are caused by a single-gene change. These types of dementia can be directly inherited from parent to child.

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