5. FTD and Genetic Links
Delving into the genetic underpinnings of Frontotemporal Dementia adds another layer of complexity to this disease. While most neurodegenerative disorders have some genetic component, the influence of genetics on FTD is particularly noteworthy.
In about 10-20% of FTD cases, a clear familial pattern emerges – these cases are known as familial FTD. These instances of the disease are linked to genetic mutations passed down through families, and a mutation in one of several genes significantly raises the risk of developing FTD. Three genes are particularly prominent in familial FTD – the MAPT gene, the GRN gene, and the C9orf72 gene.
The MAPT gene provides instructions for making a protein called tau, found in neurons. Specific mutations in the MAPT gene can lead to an abnormal tau protein structure that cannot stabilize the neuron’s internal skeleton as it should, leading to the death of nerve cells, a hallmark of FTD.
Similarly, the GRN gene, responsible for making progranulin, a protein involved in inflammation and wound healing, can also undergo mutations leading to FTD. Progranulin is believed to help neurons survive and function correctly. GRN mutations reduce the amount of this protective protein, making neurons vulnerable to damage and death.
In addition to MAPT and GRN, the C9orf72 gene also plays a crucial role in familial FTD. Repeated DNA sequences in this gene are the most common genetic cause of FTD. The reasons for this are still being researched, but it’s thought that the abnormal repetitions may interfere with the normal functioning of neurons.
Understanding the genetic underpinnings of FTD can be invaluable for families affected by this disease. It can provide an explanation for the disease’s occurrence and recurrence in some families, offer insight into who else in the family might be at risk, and even inform family planning decisions.
Moreover, genetic counseling and testing can be a valuable tool in managing familial FTD. Individuals who have FTD in their family history can explore these options, potentially allowing for earlier intervention and better management of the disease. It’s crucial to underscore that genetic testing is a complex process and should be undertaken with proper guidance from healthcare professionals.(5)
