There have been some stories in the news recently about buying kits that can tell you about your genetic makeup. These kits include testing for genes that can influence your risk of developing certain conditions, including Alzheimer's disease. However, the genetics behind Alzheimer's disease and other forms of dementia is complex and these kits cannot tell the complete story about a person's risk of developing the condition.
The most widely available DNA kits that offer testing for genes related to disease are from a company called 23andme, although other companies do also offer similar services. The 23andme kit costs £149 and can be purchased online or in some retail outlets. The buyer provides a DNA sample using a saliva swab, which is then posted to a testing lab.
The list of genes that the company looks for is extensive and includes genes linked to several conditions, including breast cancer, Parkinson's disease and cystic fibrosis. They also offer a service that investigates your genetic ancestry.
23andme were banned by the Food and Drug Administration (FDA) in the US in 2013 from marketing their genetic test as a medical product, although they were still allowed to offer the ancestry service. The company was cleared to offer testing for genes related to disease in the UK in December 2014 and given FDA approval in April 2017 to offer testing for certain medical conditions, including Alzheimer's and Parkinson's diseases.
Part of the 23andme service gives you the chance to see your 'raw data', for you to examine yourself and lists changes in hundreds of thousands different genes that could be linked to a variety of diseases. This 'raw data' does contain information relating to several rare genetic changes directly linked to younger-onset Alzheimer's disease.
The genetics of dementia
There are many different forms of dementia, of which Alzheimer's disease is the most common. Each form has different underlying causes and may have different genetic and lifestyle risk factors. There are some forms of dementia that are caused by known changes in certain genes. These forms are inherited from a parent and symptoms often develop in people in their 40s and 50s.
The most common genes that are linked to inherited forms of Alzheimer's disease are called APP, PSEN1 and PSEN2. Certain changes in these genes cause the disease because they alter the gene's function. These gene changes can be passed from parent to child.
Another form of dementia, called frontotemporal dementia, has been linked to different genetic changes, including in the MAPT, C9orf72 and GRN genes. These inherited forms of dementia account for less than 1% of all people affected by the condition.
The medical test for Alzheimer's disease from 23andme does not search for changes in any of these genes but information on them may be found in the uninterpreted 'raw' data that is available with the test.
The development of the most common form of Alzheimer's disease, which affects more than 520,000 people in the UK, has not been directly linked to a single genetic change. However, there have been almost 20 genes identified that might play a role in changing a person's likelihood of developing the condition.
The gene that is most strongly associated with the most common form of Alzheimer's is called APOE. It is the APOE gene that the 23andme kits use in their 'medical testing' analysis.
APOE and Alzheimer's disease risk
Of all the risk genes identified so far, APOE has been found to have the strongest genetic link to Alzheimer's disease. It forms part of a mechanism that transports cholesterol around the body, including in the brain.
The APOE gene has three different forms, called variants 2, 3 and 4. These variants have slight differences in their DNA patterns. Like most genes, we inherit one form of APOE from each of our parents. Inheriting variant 4 has been shown to increase risk of developing Alzheimer's disease, with the greatest risk occurring for those who inherit two copies. The variant 2 form of the gene has been linked to a slightly reduced risk. This is due to the changes in the genes having different effects on the way that the gene behaves. The reason behind why these changes influence Alzheimer's development is so far unclear.
Inheriting one or two copies of APOE variant 4 does not mean that you will definitely develop Alzheimer's. It just means that you are more likely to develop the condition than someone who does not have any copies of APOE variant 4. Conversely, inheriting variants 2 or 3 of the gene does not mean that you are protected from getting Alzheimer's disease.
It is likely that a combination of several different genes determines your risk of being affected by the common form of Alzheimer's disease. The self-testing kits do not check for any of these other risk genes.
The risk of developing Alzheimer's disease is complex and involves other factors alongside genetics. The strongest risk factor by far is age, with the likelihood of being affected increasing as we get older. Other risk factors include diet, exercise, smoking, alcohol intake and depression. However, this list is not exhaustive and researchers are continuing to investigate the roles that these and other risk factors have with regards to dementia development.
Learning about your APOE type will give you an idea of your risk of developing Alzheimer's disease but will not accurately say whether you will develop the condition or not. These tests do not take into account other risk factors such as other genetic links and environmental influence. It also does not discount the possibility of developing other inherited forms of dementia.
Genetic tests for dementia on the NHS
The NHS offers genetic testing for people believed to be at risk of an inherited form of dementia, for example frontotemporal dementia or some forms of younger-onset Alzheimer's disease. This includes people who have a close relative who has been shown to have an inherited form of the condition or people with several relatives developing dementia when they are younger than 65 years of age. In these cases, genetic counselling is available if required, both before the test is taken and after the results. The self-testing kits do not offer any form of pre-test genetic counselling and don't directly offer customers counselling after they are tested.
Due to the complex risk factors that lie behind the more common form of Alzheimer's disease, the NHS does not offer a genetic test for it. The NHS does not test for APOE type or use this as a basis for diagnosis.