biostudies-literatureUnknownRiordan RBLRD VANIA NIH HHSNINDS NIH HHSNIH HHSGenetic variation in the lysosomal and transmembrane protein 106B (TMEM106B) modifies risk for a diverse range of neurodegenerative disorders, especially frontotemporal lobar degeneration (FTLD) with progranulin (PGRN) haplo-insufficiency, although the molecular mechanisms involved are not yet understood. Through advances in cryo-electron microscopy (cryo-EM), homotypic aggregates of the C-Terminal domain of TMEM106B (TMEM CT) were discovered as a previously unidentified cytosolic proteinopathy in the brains of FTLD, Alzheimer's disease, progressive supranuclear palsy (PSP), and dementia with Lewy bodies (DLB) patients. While it remains unknown what role TMEM CT aggregation plays in neuronal loss, its presence across a range of aging related dementia disorders indicates involvement in multbioRxiv : the preprint server for biology2024.06.11.598478https://www.ebi.ac.uk/biostudies/studies/S-EPMC11195232biostudies-literatureTMEM106B C-terminal fragments aggregate and drive neurodegenerative proteinopathy.PMC11195232I01 BX004044R01 AG066729P40 OD010440R01 NS064131IK6 BX006467Saxton ALiachko NFKow RLKraemer BCRiordan RMcMillan PJfalseTMEM106B C-terminal fragments aggregate and drive neurodegenerative proteinopathy.Genetic variation in the lysosomal and transmembrane protein 106B (TMEM106B) modifies risk for a diverse range of neurodegenerative disorders, especially frontotemporal lobar degeneration (FTLD) with progranulin (PGRN) haplo-insufficiency, although the molecular mechanisms involved are not yet understood. Through advances in cryo-electron microscopy (cryo-EM), homotypic aggregates of the C-Terminal domain of TMEM106B (TMEM CT) were discovered as a previously unidentified cytosolic proteinopathy in the brains of FTLD, Alzheimer's disease, progressive supranuclear palsy (PSP), and dementia with Lewy bodies (DLB) patients. While it remains unknown what role TMEM CT aggregation plays in neuronal loss, its presence across a range of aging related dementia disorders indicates involvement in mult2024-01-01T00:00:00Z2024 Jun2025-09-01T03:16:40.524Z2025-09-01T03:08:29.942ZS-EPMC111952323891559810.1101/2024.06.11.598478