ArticleEMBO reports2021
FTLD-TDP assemblies seed neoaggregates with subtype-specific features via a prion-like cascade.
Article in EMBO reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- TDP-43 Aggregation: The Healthy-Toxic Balance of the Prion-Like Domain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- TDP-43 Acetylation at the Neuroimmune Interface: A Hypothesis-Driven Framework for Peripheral Inflammatory Stratotypes in ALS.Neurochemical research · 2026Review
- Somatic mosaicism in ALS and FTD identifies focal mutations associated with widespread degeneration.Nature genetics · 2026Article
- Cracking the code of native amyloid fibrils: advances and next steps to enable pathology-informed therapeutic and diagnostic.Nature structural & molecular biology · 2026Review
- Lysosomal escape and TMEM106B fibrillar core determine TDP-43 seeding outcomes.bioRxiv : the preprint server for biology · 2025Article
- Direct interaction between TDP-43 and Tau promotes their co-condensation, while suppressing Tau fibril formation and seeding.The EMBO journal · 2025Article
- Correlative light and electron microscopy for human brain and other biological models.Nature protocols · 2025Review
- RNA-binding proteins in ALS and FTD: from pathogenic mechanisms to therapeutic insights.Molecular neurodegeneration · 2025Review
- Prion-like Spreading of Disease in TDP-43 Proteinopathies.Brain sciences · 2024Review
- Frontotemporal dementia-like disease progression elicited by seeded aggregation and spread of FUS.Molecular neurodegeneration · 2024Article
- Article
- "Prion-like" seeding and propagation of oligomeric protein assemblies in neurodegenerative disorders.Frontiers in neuroscience · 2024Review
- Loss of TDP-43 oligomerization or RNA binding elicits distinct aggregation patterns.The EMBO journal · 2023Article
- Article
- Emerging Trends in the Field of Inflammation and Proteinopathy in ALS/FTD Spectrum Disorder.Biomedicines · 2023Review
- Tandem detergent-extraction and immunoprecipitation of proteinopathy: Scalable enrichment of ALS-associated TDP-43 aggregates.iScience · 2023Article
- Distinguishing post-translational modifications in dominantly inherited frontotemporal dementias: FTLD-TDP Type A (GRN) vs Type B (C9orf72).Neuropathology and applied neurobiology · 2022Article
- miRNA Expression Is Increased in Serum from Patients with Semantic Variant Primary Progressive Aphasia.International journal of molecular sciences · 2022Article
- Ultrastructural and biochemical classification of pathogenic tau, α-synuclein and TDP-43.Acta neuropathologica · 2022Review
- FTLD-TDP assemblies seed neoaggregates with subtype-specific features via a prion-like cascade.EMBO reports · 2021Article
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Morphologically distinct TDP-43 aggregates occur in clinically different FTLD-TDP subtypes, yet the mechanism of their emergence and contribution to clinical heterogeneity are poorly understood. Several lines of evidence suggest that pathological TDP-43 follows a prion-like cascade, but the molecular determinants of this process remain unknown. We use advanced microscopy techniques to compare the seeding properties of pathological FTLD-TDP-A and FTLD-TDP-C aggregates. Upon inoculation of patient-derived aggregates in cells, FTLD-TDP-A seeds amplify in a template-dependent fashion, triggering neoaggregation more efficiently than those extracted from FTLD-TDP-C patients, correlating with the respective disease progression rates. Neoaggregates are sequentially phosphorylated with N-to-C directionality and with subtype-specific timelines. The resulting FTLD-TDP-A neoaggregates are large and contain densely packed fibrils, reminiscent of the pure compacted fibrils present within cytoplasmic inclusions in postmortem brains. In contrast, FTLD-TDP-C dystrophic neurites show less dense fibrils mixed with cellular components, and their respective neoaggregates are small, amorphous protein accumulations. These cellular seeding models replicate aspects of the patient pathological diversity and will be a useful tool in the quest for subtype-specific therapeutics.
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Registered trials
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