Preprint: Granulin loss and TMEM106B risk converge on lysosomal C-terminal fragment pathology in frontotemporal dementia
WHY IT MATTERS
If you or a family member carries a GRN mutation, understanding how TMEM106B variants modify your risk could eventually help doctors predict who will develop frontotemporal dementia and when, potentially enabling earlier monitoring or future preventive treatments.
Scientists are studying how two genes work together to cause frontotemporal dementia, a type of brain disease that affects thinking and behavior. One gene called GRN normally makes a protein that protects brain cells, but when it's broken, people can develop dementia. Another gene called TMEM106B can either increase or decrease the risk of getting sick. This research helps explain why some people with the broken GRN gene stay healthy their whole lives while others get dementia.
Granulin loss and TMEM106B risk converge on lysosomal C-terminal fragment pathology in frontotemporal dementia Authors: Zeng, Y. et al. Server: bioRxiv Category: genetics Abstract: Frontotemporal dementia (FTD) is the second most common cause of dementia after Alzheimer disease. Mutations in GRN, which encodes progranulin, are a major cause of FTD. Common genetic variants in the TMEM106B gene modify risk of FTD and the effect is especially strong in GRN mutation carriers. Intriguingly, in GRN mutation carriers, being homozygous for the protective TMEM106B haplotype seems to confer near lifetime protection against FTD. Despite the strong genetic link between GRN and TMEM106B, how these two genes interact mechanistically has remained unresolved. Recent studies have reveale