ArticleNeuropathology and applied neurobiology2015
Accumulation of dipeptide repeat proteins predates that of TDP-43 in frontotemporal lobar degeneration associated with hexanucleotide repeat expansions in C9ORF72 gene.
Article in Neuropathology and applied neurobiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- The imaging signature of C9orf72 hexanucleotide repeat expansions: implications for clinical trials and therapy development.Brain imaging and behavior · 2021Pooled it
- Intrathecal (GActa neuropathologica communications · 2026Article
- The molecular mechanism of uptake and cell-to-cell transmission of arginine-containing dipeptide repeat proteins.bioRxiv : the preprint server for biology · 2025Article
- C9ORF72 poly-PR disrupts expression of ALS/FTD-implicated STMN2 through SRSF7.Acta neuropathologica communications · 2025Article
- Article
- ALS' Perfect Storm:Cells · 2024Review
- Distinct neuroinflammatory signatures exist across genetic and sporadic amyotrophic lateral sclerosis cohorts.Brain : a journal of neurology · 2023Article
- Random forest modelling demonstrates microglial and protein misfolding features to be key phenotypic markers in C9orf72-ALS.The Journal of pathology · 2022Article
- Hyperactivity of Purkinje cell and motor deficits in C9orf72 knockout mice.Molecular and cellular neurosciences · 2022Article
- Interactome screening of C9orf72 dipeptide repeats reveals VCP sequestration and functional impairment by polyGA.Brain : a journal of neurology · 2022Article
- Modelling amyotrophic lateral sclerosis in rodents.Nature reviews. Neuroscience · 2022Review
- Proximity proteomics of C9orf72 dipeptide repeat proteins identifies molecular chaperones as modifiers of poly-GA aggregation.Acta neuropathologica communications · 2022Article
- C9orf72-derived arginine-rich poly-dipeptides impede phase modifiers.Nature communications · 2021Article
- Inducible expression of humanDisease models & mechanisms · 2021Article
- Emerging Perspectives on Dipeptide Repeat Proteins in C9ORF72 ALS/FTD.Frontiers in cellular neuroscience · 2021Review
- Fluid Biomarkers of Frontotemporal Lobar Degeneration.Advances in experimental medicine and biology · 2021Article
- Arginine-rich dipeptide-repeat proteins as phase disruptors in C9-ALS/FTD.Emerging topics in life sciences · 2020Review
- Glycine-alanine dipeptide repeats spread rapidly in a repeat length- and age-dependent manner in the fly brain.Acta neuropathologica communications · 2019Article
- FDG-PET underscores the key role of the thalamus in frontotemporal lobar degeneration caused by C9ORF72 mutations.Translational psychiatry · 2019Article
- C9orf72-FTD/ALS pathogenesis: evidence from human neuropathological studies.Acta neuropathologica · 2019Review
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
aimsFrontotemporal lobar degeneration (FTLD) and motor neurone disease are linked by the possession of a hexanucleotide repeat expansion in C9ORF72, and both show neuronal cytoplasmic inclusions within cerebellar and hippocampal neurones which are TDP-43 negative but immunoreactive for p62 and dipeptide repeat proteins (DPR), these being generated by a non-ATG RAN translation of the expanded region of the gene.
methodsTwenty-two cases of FTLD from Newcastle were analysed for an expansion in C9ORF72 by repeat primed PCR and Southern blot. Detailed case note analysis was performed, and blinded retrospective clinical impressions were achieved by review of clinical histories. Sections from all major brain regions were immunostained for TDP-43, p62 and DPR. The extent of TDP-43 and DPR pathology in expansion bearers was compared with that in 13 other previously identified cases from the Manchester Brain Bank with established disease.
resultsThree Newcastle patients bearing an expansion in C9ORF72 were identified. These three patients died prematurely, two from bronchopneumonia within 10 months and 3 years of onset, and one from myocardial infarction 3 years after onset. In all three, DPR were plentiful throughout all cerebral cortical regions, hippocampus and cerebellum, but TDP-43 pathological changes were sparse. The severity of DPR pathological changes in these three patients was similar to that in the Manchester series, although the extent of TDP-43 pathology was significantly less.
conclusionWidespread accumulation of DPR within nerve cells may occur much earlier than that of TDP-43 in patients with FTLD bearing expansion in C9ORF72.
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