Expert Reviewed By: Dr. Brandon Colby MD
Frontotemporal dementia (FTD) is a group of neurodegenerative disorders characterized by progressive deterioration of the frontal and temporal lobes of the brain. One specific type of FTD, known as frontotemporal dementia with TDP43 inclusions (TARDBP-related), has gained attention in recent years due to advances in genetic testing and molecular research. This article aims to provide a comprehensive understanding of TARDBP-related FTD, its diagnosis, and the role of genetic testing in this disease.
What is TARDBP-Related Frontotemporal Dementia?
TARDBP-related FTD is a subtype of frontotemporal dementia characterized by the presence of abnormal protein aggregates, called TDP43 inclusions, in the brain. These inclusions are primarily composed of the TDP-43 protein, which plays a crucial role in regulating gene expression. The presence of TDP43 inclusions has been linked to various neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and some forms of FTD. The clinical, genetic, and pathological overlap between these diseases has been highlighted in recent research, such as the study by Molecular basis of ALS and FTD: implications for translational studies.
Diagnosing TARDBP-Related FTD
Diagnosing TARDBP-related FTD can be challenging due to the overlap of symptoms with other forms of FTD and neurodegenerative diseases. However, recent advances in genetic testing have made it possible to identify the presence of TARDBP gene mutations, which can help confirm a diagnosis of TARDBP-related FTD. Genetic testing can also provide valuable information for family members who may be at risk of developing the disease.
Uses of Genetic Testing for TARDBP-Related FTD
Genetic testing can play a vital role in the diagnosis and management of TARDBP-related FTD. Some of the key uses of genetic testing for this disorder include:
- Confirming a diagnosis: Identifying a mutation in the TARDBP gene can help confirm a diagnosis of TARDBP-related FTD in individuals with symptoms suggestive of the disease.
- Identifying at-risk family members: Genetic testing can be used to identify family members who carry a TARDBP gene mutation and may be at risk of developing the disease. This information can help individuals make informed decisions about their health and plan for the future.
- Guiding treatment and management: Understanding the genetic basis of TARDBP-related FTD can help guide treatment decisions and inform the development of targeted therapies. For example, a recent study titled Reduction of nemo-like kinase increases lysosome biogenesis and ameliorates TDP-43-related neurodegeneration identified a potential therapeutic target for multiple neurodegenerative disorders, including TARDBP-related FTD.
Recent Advances in TARDBP-Related FTD Research
Research into the molecular mechanisms of TARDBP-related FTD has led to significant advances in our understanding of the disease. One such study, Reduction of Nemo-like kinase increases lysosome biogenesis and ameliorates TDP-43-related neurodegeneration, has identified nemo-like kinase (Nlk) as a negative regulator of lysosome biogenesis. By reducing Nlk levels, researchers were able to improve the clearance of aggregated TDP-43 and ameliorate pathological, behavioral, and life span deficits in mouse models of TDP-43 proteinopathy. This finding suggests a potential therapy for TARDBP-related FTD and other neurodegenerative disorders.
Conclusion
TARDBP-related frontotemporal dementia is a complex and challenging disease, but advances in genetic testing and molecular research are shedding light on its underlying mechanisms and potential treatments. By understanding the role of the TARDBP gene and TDP43 inclusions in the disease, clinicians and researchers can work towards developing targeted therapies and improving the lives of those affected by TARDBP-related FTD.
About The Expert Reviewer
Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of and the author of Outsmart Your Genes.
Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (ACMG), an Associate of the American College of Preventive Medicine (ACPM), and a member of the National Society of Genetic Counselors (NSGC)