In the second part of our blog series on dementia risk, Research Communications Officer Louise Walker explains more about the genetics of dementia.
‘Is dementia hereditary?’ is one of the most frequent questions that we receive here in the Research team at Alzheimer’s Society and is one of the most searched-for terms on the Research part of our website. However, as with many things in research, there is no simple answer!
There are many different forms of dementia and each form has its own underlying causes, including genetics. For the majority of cases, genes do play a part but are not the whole story. However, there are some rare forms of dementia which have a known genetic link.
In this blog I’ll explain a little more about what we know about the genetics of various forms of dementia.
Researchers and doctors often split Alzheimer’s disease into two categories. These are known as ‘later-onset’ and ‘early-onset’ or ‘younger-onset’. The later-onset version of the condition is by far the more common and is usually diagnosed in people over the age of 65; those under 65 are usually diagnosed as having ‘younger-onset Alzheimer’s disease’. As well as age, these two forms can sometimes be distinguished by differences in their genetics.
Younger-onset Alzheimer’s disease
Some cases of younger-onset Alzheimer’s disease have a known genetic component. These cases are sometimes called ‘Familial Alzheimer’s disease’.
Changes in genes called APP, PSEN1 and PSEN2 are known to cause the disease directly. This is because these genes are involved in the formation of the Alzheimer’s hallmark amyloid clumps, which are found in the brains of people with the disease.
The changes in the APP, PSEN1 and PSEN2 genes are very rare, and account for less than 1% (1 in 100) of all cases of Alzheimer’s disease.
If a doctor suspects a person may have an inherited form of the condition, either by family history or by developing the condition at a very early age (in your 30s, 40s or 50s), the person may be offered genetic testing. Their relatives may also be offered genetic testing. In these cases, genetic counselling will be offered if the person is found to carry the disease-related changes
Later-onset Alzheimer’s disease
‘Later-onset’ Alzheimer’s disease is the most common form of dementia, affecting around 520,000 people in the UK. Despite this form of Alzheimer’s disease also involving the amyloid protein, the APP, PSEN1 and PSEN2 genes have not been found to have a strong link to the development of this form of the condition.
There are some genes that are associated with increased risk of later-onset Alzheimer’s disease. The strongest known genetic risk factor is a gene called ApoE. You inherit one copy of ApoE from each parent and ApoE can exist in one of three forms – ApoE2, ApoE3 and ApoE4. If you have one or two copies of the ApoE4 version, this can increase your risk. However, having ApoE4 does not mean you’ll definitely develop dementia.
ApoE4 is the gene that most commercial ‘genetic testing’ kits are looking for when it comes to Alzheimer’s disease, but these tests cannot tell you whether you are going to develop dementia or not.
There are a number of other rare changes in certain genes that are each thought to contribute a little bit towards a person’s risk of the most common form of Alzheimer’s. Researchers believe it may be a combination of several genes exerting a small effect, along with other factors such as lifestyle, which will influence a person’s risk of developing this form of Alzheimer’s disease.
What this all boils down to is that having a family member with Alzheimer’s disease could mean that you are at an increased risk, but this alone isn’t enough to know whether you will go on to develop the disease.
Frontotemporal dementia is a form that often affects people in their 40s and 50s. Like younger-onset Alzheimer’s disease, some forms of frontotemporal dementia have a known genetic component.
The genes that are associated with frontotemporal dementia are called MAPT (which is associated with toxic tangles of the protein tau), progranulin (also called GRN) and C9orf72. The changes in these genes can be passed from parent to child and so genetic testing may be offered if a parent develops frontotemporal dementia. However, like younger-onset Alzheimer’s disease, not everyone with frontotemporal dementia has changes in these genes so having a parent with the condition doesn’t mean their children will definitely develop it.
What does this mean for me?
As you can see, the genetics of dementia are complicated. Certain forms can be inherited from a parent, and those with younger-onset dementia are more likely to have genetic versions of the condition. However, even in these cases the cause isn’t always clear-cut.
If you have a family member with younger-onset dementia or a known genetic form of the condition, you should be offered genetic testing. It is a very personal decision whether you undergo genetic testing and you should be offered counselling as part of the test. You may also be interested in a project called ‘100,000 genomes’, which aims to understand more about these genetic forms of dementia.
When it comes to the more common form of Alzheimer’s disease and other forms of dementia such as dementia with Lewy bodies and vascular dementia, the genetic influences are less well-known. At the moment, it is generally not possible to tell from a genetic test whether you will develop these conditions.
When it comes to dementia risk, we can’t control our genes but there are other elements we can control that could help to reduce risk. This includes not smoking, eating a healthy, balanced diet and managing conditions such as diabetes.