Jordan D Marks, Virginia Estades Ayuso, Yari Carlomagno, Mei Yue, Tiffany W Todd, Ying Hao, Ziyi Li, Zachary T McEachin, Anantharaman Shantaraman, Duc M Duong, Lillian M Daughrity, Karen Jansen-West, Wei Shao, Anna Calliari, Jesus Gonzalez Bejarano, Michael DeTure, Bailey Rawlinson, Monica Castanedes Casey, Meredith T Lilley, Megan H Donahue, Vidhya Maheswari Jawahar, Bradley F Boeve, Ronald C Petersen, David S Knopman, Björn Oskarsson, Neill R Graff-Radford, Zbigniew K Wszolek, Dennis W Dickson, Keith A Josephs, Yue A Qi, Nicholas T Seyfried, Michael E Ward, Yong-Jie Zhang, Mercedes Prudencio, Leonard Petrucelli, Casey N Cook
Genetic variation at the transmembrane protein 106B gene ( TMEM106B) has been linked to risk of frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) through an unknown mechanism. We found that presence of the TMEM106B rs3173615 protective genotype was associated with longer survival after symptom onset in a postmortem FTLD-TDP cohort, suggesting a slower disease course. The seminal discovery that filaments derived from TMEM106B is a common feature in aging and, across a range of neurodegenerative disorders, suggests that genetic variants in TMEM106B could modulate disease risk and progression through modulating TMEM106B aggregation...
January 17, 2024: Science Translational Medicine