The Intersection of TMEM106B Fibrils, TDP-43 Pathology & Lysosomal Function in Neurodegeneration

  • How TMEM106B genetic variants modulate ALS–FTD risk and intersect with progranulin-dependent lysosomal biology
  • Developed a model system of TMEM106B aggregation that leads to intra-lysosomal fibril formation in human neurons
  • Evidence that TMEM106B aggregation induces elevated levels of phospho-TDP-43
  • Direct co-localization of TMEM106B fibrils and TDP-43 aggregates within individual lysosomes
  • Implications of TMEM106B-driven lysosomal failure as an upstream, targetable mechanism across neurodegenerative diseases