Genetics of dementia

4. Frontotemporal dementia (FTD)

Frontotemporal dementia (FTD) quite often runs in families, especially the behavioural form of the condition. Of the four most common dementias, FTD is the one in which genes have the largest impact.

Familial frontotemporal dementia

About 10-15 per cent of people with FTD have a very strong family history of the condition. This means having three or more relatives with FTD across at least two generations.

A similar number of people with FTD have a weaker family history of dementia, but not necessarily of frontotemporal dementia.

In up to 30 per cent of all people with FTD, the condition is known to be caused by a mutation in a single gene. At least eight genes - including some with very rare mutations - are so far known to cause FTD, and more are likely to be discovered. Of the different types of FTD, the behavioural form - the most common form of FTD - is the one that is inherited most often. Semantic dementia, in contrast, is only rarely inherited.

Most familial frontotemporal dementia is caused by mutations in three genes. These are a recently discovered gene called C9ORF72, and genes for the proteins tau (MAPT) and progranulin (GRN). The particular mutation that a person has tends to influence their symptoms. For example, C9ORF72 is linked to both FTD and motor neurone disease and some affected families have a history of both conditions.

If someone has one of these faulty genes, then each of their children has a 50 per cent chance of inheriting the mutation. Each sibling of someone with the mutation also has a 50 per cent chance of having inherited the mutation. As with familial Alzheimer's disease, nearly everyone who inherits the mutation will develop FTD, with the exception of C9ORF72. For reasons that are not clear, some people have the C9ORF72 mutation but do not go on to develop FTD.

Risk genes for frontotemporal dementia

In the past few years, researchers have begun to look for 'risk genes' (acting like APOE) for FTD. For example, variants in a gene called TMEM106B affect someone's chances of developing FTD.