The role of somatic TARDBP variants in the pathogenesis of semantic dementia


  • Two pathogenic somatic variants of the TARDBP gene (L41F and R42H) were detected in the brains of individuals with semantic dementia and were shown to alter the localization and RNA splicing function of the TDP-43 protein.

Why this matters

    The presence of somatic variants in cases of semantic dementia indicates that germline variant testing may be insufficient to determine pathogenesis for other neurodegenerative diseases.