Hello and welcome to the Wicking Dementia Laboratory, where one of the things we are working to understand is the genetics of dementia. When someone in their family has dementia, people are naturally concerned about whether it can be inherited. The genetics of dementia is complex and not fully understood. However, we do know that the vast majority of cases of dementia is not caused by an inherited genetic mutation. Dementia is so common that having several close relatives with dementia is not evidence of a genetic link.
There are a few gene mutations we know about that do cause dementia, however. So for a very small number of families, dementia can be inherited when the mutation is passed on. In these rare genetic forms of dementia, the onset is usually at a younger age, in the 40s or 50s.
Let’s meet one of those families. This is the Appleton family.
This is Alan Appleton, and he has familial Alzheimer’s disease. He inherited a faulty gene that causes Alzheimer’s from his mother, who also had the disease.
Three genes have been identified which, if mutated in certain ways, will cause familial Alzheimer’s disease. The mutation causing Alan’s Alzheimer’s is in a gene called APP.
We inherit half our genes from our mother and half from our father. While Alan inherited a faulty copy of the APP gene from his mother, he also inherited a normal copy from his father.
This is Alice, Alan’s partner. Her mother also had Alzheimer’s disease, but it was the common sporadic type, so Alice has two normal copies of the APP gene.
Meet April and Augustus, Allan and Alice’s children. When someone carries a faulty gene that causes dementia, there is a 50-50 chance they will pass it on to their child, because they could pass on either their faulty or normal copy of the gene.
April inherited the normal APP gene from her father and from her mother, so she will not get familial Alzheimer’s disease. She could still get sporadic Alzheimer’s disease, but she is at no greater risk than anyone else in the population.
Augustus on the other hand, inherited the faulty APP gene from his father and a normal gene from his mother. He will develop familial Alzheimer’s disease because the mutated gene is dominant over the normal copy.
Genetic forms of Alzheimer’s disease like the one affecting Alan and Augustus Appleton account for only around 1% of cases. So the vast majority of cases are sporadic, which means their cause is unknown. There are also other gene mutations that can cause other types of dementia, but for all the common causes of dementia, most cases are not inherited.
So what about the sporadic forms of dementia, do genes play a role there? Research shows that, on average, people who have a close relative with a sporadic form of dementia have an increased risk of developing the condition, compared to someone without that family history. The increase in risk is similar to the increase we see for other risk factors like diabetes or smoking. And it is likely due to a combination of genetic and environmental influences on our risk of dementia.
One of the genetic influences on our risk of Alzheimer’s disease is a gene called APOE. This gene comes in three normal variations. APOE3 is the most common variation, and doesn’t influence our risk of Alzheimer’s disease. APOE2 is associated with reduced risk, while APOE4 is known to increase the risk.
对我们患阿尔茨海默病的风险的遗传影响之一是称为APOE的基因。这个基因有三种常见的变异类型。 APOE3是最常见的变异，并不影响我们患阿尔茨海默病的风险。 APOE2与降低的风险相关，而APOE4已知会增加风险。
APOE4 does not cause Alzheimer’s, it only increases the risk of it developing. Some people with APOE4 never develop Alzheimer’s disease, and others who develop Alzheimer’s do not have APOE4. So even if someone has the APOE4 gene, it is impossible to predict whether or not they will develop dementia, but they are at increased risk.
In addition to APOE4, many other genes have been identified that have smaller effects on the risk of dementia. We are each born with an individual mix of genes, some of which may reduce our risk of dementia while others may increase it. At this time, it is not possible to measure any person’s individual genetic risk for dementia.
Thanks for visiting the Wicking Dementia Laboratory and I hope you’ve enjoyed learning about the genetics of dementia.