ArticleBrain : a journal of neurology2020
Somatic TARDBP variants as a cause of semantic dementia.
Article in Brain : a journal of neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- Somatic mosaicism in the brain: linking development, ageing and neurodegeneration.Nature reviews. Neurology · 2026Review
- RNA-binding proteins in ALS and FTD: from pathogenic mechanisms to therapeutic insights.Molecular neurodegeneration · 2025Review
- Microbial Trojan Horses: Virulence Factors as Key Players in Neurodegenerative Diseases.Molecules (Basel, Switzerland) · 2025Review
- Prion-like Spreading of Disease in TDP-43 Proteinopathies.Brain sciences · 2024Review
- Frontotemporal lobar degeneration.Nature reviews. Disease primers · 2023Review
- Frontotemporal Degeneration with Transactive Response DNA-Binding Protein Type C at the Anterior Temporal Lobe.Annals of neurology · 2023Review
- Weighted gene co-expression network analysis reveals the hub genes associated with pulmonary hypertension.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Proteomics of the dentate gyrus reveals semantic dementia specific molecular pathology.Acta neuropathologica communications · 2022Article
- Neurocognitive patterns across genetic levels in behavioral variant frontotemporal dementia: a multiple single cases study.BMC neurology · 2022Article
- The Neurogenetics Collection: emerging themes and future considerations for the field in Brain.Brain : a journal of neurology · 2022Article
- Genetic mosaicism in the human brain: from lineage tracing to neuropsychiatric disorders.Nature reviews. Neuroscience · 2022Review
- Primary progressive aphasia and motor neuron disease: A review.Frontiers in aging neuroscience · 2022Review
- Somatic mutations may contribute to asymmetry in neurodegenerative disorders.Brain communications · 2022Article
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aetiology of late-onset neurodegenerative diseases is largely unknown. Here we investigated whether de novo somatic variants for semantic dementia can be detected, thereby arguing for a more general role of somatic variants in neurodegenerative disease. Semantic dementia is characterized by a non-familial occurrence, early onset (<65 years), focal temporal atrophy and TDP-43 pathology. To test whether somatic variants in neural progenitor cells during brain development might lead to semantic dementia, we compared deep exome sequencing data of DNA derived from brain and blood of 16 semantic dementia cases. Somatic variants observed in brain tissue and absent in blood were validated using amplicon sequencing and digital PCR. We identified two variants in exon one of the TARDBP gene (L41F and R42H) at low level (1-3%) in cortical regions and in dentate gyrus in two semantic dementia brains, respectively. The pathogenicity of both variants is supported by demonstrating impaired splicing regulation of TDP-43 and by altered subcellular localization of the mutant TDP-43 protein. These findings indicate that somatic variants may cause semantic dementia as a non-hereditary neurodegenerative disease, which might be exemplary for other late-onset neurodegenerative disorders.
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