An international genetic study implicates a role for the immune system in FTD

In a tour de force, 44 international research groups worked together to perform a genome-wide association study to identify novel genetic risk factors for FTD using DNA samples from 3526 patients with FTD and 9402 healthy control individuals. Their work suggests that the immune system and biological pathways involved in the breakdown of proteins and cellular debris may play a role in FTD.

In genome-wide association studies hundreds of thousands of genetic variants are studied at once to identify which variants occur at a higher frequency in patients compared with controls. This popular approach to the identification of genetic risk factors has been successfully used in recent years to identify risk factors for a number of neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease and Amyotrophic Lateral Sclerosis/Motor Neurone Disease. However, no such study had been performed in patients clinically diagnosed with FTD until now. This new study implicates two novel regions in FTD, one location or ‘locus’ on chromosome 6 contains the gene called HLA and another locus on chromosome 11 contains the genes RAB38 and CTSC.

HLA is responsible for the generation of proteins on the surface of cells that are responsible for the regulation of the immune system. The identification of a genetic association of FTD with the HLA locus therefore points to a link between FTD and the immune system. The RAB38/CTSC locus produces proteins related to lysosomes (the part of our cells important for digesting unwanted materials) as well as inflammatory processes. Further studies suggested that the genetic variants that increase the risk for FTD at the RAB38/CTSC locus may be associated with decreased function in the RAB38 gene.

The identification of novel genes that increase risk for FTD is important to further our understanding of the pathological mechanisms that underlie FTD, and a crucial step towards the development of future treatments. Future studies are now needed not only to confirm these genetic findings in additional FTD patient populations but also to tease out the exact role that these genes and the proteins they produce play in FTD.


Ferrari R, Hernandez DG, Nalls MA et al. Frontotemporal dementia and its subtypes: a genome-wide association study.Lancet Neurol. 2014;13(7):686-99.

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