From the Research
TMEM106B is a genetic risk factor for frontotemporal dementia (FTD), particularly in patients with progranulin (GRN) mutations or TDP-43 pathology, as evidenced by a genome-wide association study 1. The TMEM106B gene encodes a transmembrane protein found in lysosomes and endosomes, and certain variants of this gene can increase susceptibility to FTD by approximately 1.5-3 times. Key points to consider:
- The protective allele (T) helps maintain normal lysosomal function, while the risk allele (C) may disrupt lysosomal trafficking and degradation pathways, leading to protein accumulation 2.
- This is particularly important in FTD because many forms involve abnormal protein aggregation.
- Currently, TMEM106B testing is primarily used in research settings rather than clinical practice, as it indicates risk but doesn't definitively predict disease development.
- There are no specific treatments targeting TMEM106B, but understanding its role may help identify patients at higher risk and could inform future therapeutic approaches.
- For patients with family history of FTD, genetic counseling is recommended before pursuing any genetic testing, as results have implications for both the individual and their relatives. The most recent and highest quality study on this topic was published in 2016, which found that increased expression of TMEM106B causes C9orf72-dependent alterations in lysosomes 2. Other studies have also investigated the role of TMEM106B in FTD, including its regulation by the microRNA-132/212 cluster and its effects on progranulin pathways 3. However, the 2016 study provides the most up-to-date and comprehensive understanding of the relationship between TMEM106B and FTD. In terms of treatment, pharmacological options such as selective serotonin reuptake inhibitors (SSRIs) and trazodone may be effective in reducing some behavioral symptoms of FTD, but none have been shown to impact cognition 4. Overall, TMEM106B is an important genetic risk factor for FTD, and further research is needed to fully understand its role in the disease and to develop effective therapeutic strategies.