Genetics of Frontotemporal Dementia
Frontotemporal dementia has a genetic component, with less than half of the cases having a family history of the disease. Specific gene mutations, such as those in the MAPT, GRN, and C9orf72 genes, have been linked to the disease.
If your parent has frontotemporal dementia, genetic testing and counselling can provide more information about your risk.
What is Frontotemporal dementia?
Frontotemporal dementia (FTD) is a group of neurodegenerative diseases.
It results from a progressive loss of neurons in the frontal and temporal lobes of the brain. Such loss results in characteristic symptoms of the disease, like deficits in behaviour, executive function, or language. Unfortunately, these symptoms mimic other psychiatric disorders, and the disease is often misdiagnosed [1].
The disease progressively worsens.
FTD is a common type of dementia that we observe in patients younger than 65 years old [1]. Early symptoms of the disease appear relatively early, even between the ages of 40-60 and progressively worsen [2, 3]. Approximately 15-22 out of 100.000 individuals are affected annually [2, 3].
Despite the devastating impact of FTD, as is the case for many neurodegenerative diseases, there is currently no cure for FTD. The only treatment that can be administered is to improve the quality of life or manage the symptoms. An example of such may be speech therapy [1].
However, the researchers are working hard to understand the molecular basis of FTD so that different therapies may be tested and implemented if possible [1].
What Is The Genetic Link To Frontotemporal Dementia?
Although FTD is often a sporadic disease, meaning that the person has no known genetic link or family history to the disease, it can also be caused by genetic mutations [4]. In fact, around 40% of all FTD cases are caused by a genetic mutation [5, 6].
The genetic form of FTD is also referred to as the familial FTD. It results from genetic mutations in:
- MAPT
- Progranulin
- C9orf72
These are the three most common mutations that account for most cases resulting in familial FTD; however, mutations in other genes that result in the disease are also present [2].
All these mutations manifest the disease in different forms, although the behavioural variant results in about half of the cases and is, therefore, the most common type [2]. It manifests as personality change and behavioural problems and is accompanied by a cognitive decline [3].
The understanding of the genetic component of the disease has been accelerated by Gneome-Wide Association Studies and Next-Generation Sequencing, which determined a strong genetic background of FTD and the genetic risk factors [7].
In addition to these genes, a study found a strong genetic correlation between FTD risk and specific brain regions, suggesting that the genetic factors influencing brain structure may also contribute to FTD risk [8].
In addition, certain tau alleles and apolipoprotein E epsilon 4 alleles (an allele is one copy of your genetic information) have also been found to increase the risk of FTD [9].
In conclusion, there is a strong genetic link to FTD, with several genes and biological processes implicated. However, the genetic picture of FTD is complex, and further research is needed to fully understand the genetic factors contributing to this disease.
Interestingly, some of these variants are found in genes involved in the endo-lysosomal pathway, the immune response, and neuronal survival. This suggests that these biological processes may play a key role in the development of FTD [7].
My Mom Has FTD. Will I Get It?
As mentioned, the strong genetic influence of FTD can be seen in the prevalence of familial FTD cases, which is around 40% [5, 6].
Tau, Progranulin, and C9orf72 mutations can explain most cases with a high family history of the disease [10, 11, 7].
Therefore, it is essential to determine the origin of the FTD in each individual to be able to answer such questions.
In every 100 cases of FTD, around 10-15 are familial, with a family history of the disease. If you have a parent with a known familial FTD mutation, you have a 1 in 2 chance of inheriting the fault gene [5, 6].
FTD's genetic complexity and components have essential implications in diagnosis and treatment and in studying the processes resulting in FTD. In turn, researchers can involve presymptomatic patients (the ones who carry an FTD mutation but have not yet shown any symptoms) and investigate the basis of FTD to develop new targeted therapies and preventative strategies.