From the Guidelines
Frontotemporal dementia (FTD) is primarily caused by genetic mutations, with the most common genetic causes being mutations in genes such as MAPT (tau protein), GRN (progranulin), and C9orf72, which lead to the buildup of abnormal proteins including tau, TDP-43, and FUS in brain cells, causing neuron damage and death particularly in the frontal and temporal lobes. The evidence suggests that about 20% of FTD cases have an autosomal-dominant genetic mutation, with C9orf72, MAPT, and GRN being the most common causative genes 1. These genetic mutations can lead to the accumulation of abnormal proteins, resulting in progressive neuron loss in specific brain regions, and ultimately causing behavioral changes, language difficulties, and cognitive decline.
Some key points to consider when evaluating the causes of FTD include:
- Genetic mutations, such as C9orf72, MAPT, and GRN, are the most common genetic causes of FTD 1
- Environmental factors, such as head trauma, certain infections, and autoimmune disorders, may also play a role in FTD development in genetically susceptible individuals
- The disease process involves progressive neuron loss in specific brain regions, leading to behavioral changes, language difficulties, and eventual cognitive decline
- FTD typically affects people between 45-65 years of age, making it a significant cause of early-onset dementia
It's worth noting that while the evidence suggests a strong genetic component to FTD, the exact causes of the disease are still not fully understood, and further research is needed to determine the underlying mechanisms and risk factors. However, based on the current evidence, genetic mutations and abnormal protein accumulation in the brain are the primary causes of FTD. Additionally, the use of biomarkers such as CSF or serum NfL, and screening for C9orf72 mutation, can be useful in distinguishing FTD from psychiatric disorders 1.
In terms of prognosis and treatment, the evidence suggests that early diagnosis and intervention are critical in managing FTD, and that a multidisciplinary approach, including specialized psychiatric assessment and careful characterization of symptoms, can help improve patient outcomes 1. However, more research is needed to develop better prognostic tools and to identify effective treatments for FTD.