Rare types of dementia caused by genetic changes

Three of the most common types of dementia have rare familial forms that are caused by single-gene changes. These include Alzheimer's disease, frontotemporal dementia and vascular dementia. Dementia with Lewy bodies (DLB) can be caused by a single-gene change, but this is extremely rare.

Familial Alzheimer’s disease

How common is familial Alzheimer's disease?

Familial Alzheimer’s disease is a type of Alzheimer’s that is caused by a single-gene change. It is very rare. Out of 100 people who have Alzheimer’s, less than 1 of those people will have it because of a single-gene change. 99 out of 100 people who have Alzheimer’s disease will have it because of genetic risk variants and non-genetic factors such as their lifestyle.

What causes familial Alzheimer's disease?

Familial Alzheimer’s disease is usually caused by a change in one of three genes. These are:

• the PSEN-1 gene
• the APP gene
• the PSEN-2 gene.

Most cases of familial Alzheimer’s (4 out of 5) are caused by a change in the PSEN-1 gene. In these cases, dementia symptoms can begin as early as 30 years of age.

In some families no change is found in any of these three genes. These families probably have a different gene change that is even rarer and is not yet known about.

Familial frontotemporal dementia (FTD)

How common is familial FTD?

In most types of dementia, the cause is very rarely a single-gene change. However, in frontotemporal dementia (FTD), single-gene changes are much more common. About 3 or 4 in every 10 people who develop FTD have it because of a single-gene change. This means that FTD often runs strongly in families, especially the behavioural form of the dementia.

What causes familial FTD?

Familial FTD has been linked to changes in at least nine genes. The most commonly affected genes are progranulin (GRN), tau (MAPT) and C9orf72.

Nearly everyone who inherits one of these changes will develop familial FTD. However, this is not always the case. Some people may carry the changed gene but not develop FTD during their lifetime.

Familial vascular dementia

How common is familial vascular dementia?

Some very rare forms of vascular dementia are caused by single-gene changes. For example, there is a rare type of vascular dementia called cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy – more commonly known as ‘CADASIL’.

What causes CADASIL?

CADASIL is caused by a change in a gene called NOTCH3. A person with CADASIL has a 1 in 2 chance of passing on the changed gene to each child they have.

Like other types of familial dementia, CADASIL tends to develop at an earlier age than the more common vascular dementia – the average age at diagnosis is about 50 years. 

Down’s syndrome and dementia

People who have Down’s syndrome are at higher risk of developing dementia, though not everyone will develop it:

• 1 in 3 people with Down's syndrome will develop dementia in their 50s.
• When over the age of 60, almost 2 in 3 people with Down’s syndrome will develop dementia.

When dementia does develop in people with Down's syndrome, it is often Alzheimer’s disease.

Why are people with Down's syndrome more likely to develop dementia?

The higher risk of dementia is linked to the extra copy of chromosome 21 that most people with Down’s syndrome have. Chromosomes are made of DNA and chromosome 21 carries the amyloid (APP) gene.

The extra chromosome means that people with Down’s syndrome have an extra copy of the APP gene. This is thought to cause a build-up of amyloid plaques in the brain which may cause Alzheimer’s disease.