TMEM106B C-Terminal fragment aggregation exacerbates α-synuclein and TDP-43 proteinopathy phenotypes.

TMEM106B C-terminal fragment aggregation shows strong neurotoxic synergy with TDP-43 and α-synuclein proteinopathy in bigenic Caenorhabditis elegans, but only mild synergy with tau.

• Why it matters: Risk variants in TMEM106B and lesion accumulation of TMEM CT suggest it may worsen dementia by interacting with other aggregated proteins, complicating therapeutic targeting.
• What they did: Using bigenic Caenorhabditis elegans expressing TMEM CT alongside α-synuclein, tau, or TDP-43, the study measured neuronal degeneration and pathogenic protein accumulation.
• The result: The findings support TMEM CT aggregation as a significant secondary contributor to neurodegenerative phenotypes driven by TDP-43 or α-synuclein, informing intervention design.

AI summary of the abstract · may contain errors · not medical advice · read the paper.