Evidence map›Paper›PMID 39548852›Full record

Observational studyAnnals of neurology2025

Elevated Cerebrospinal Fluid Ubiquitin Carboxyl-Terminal Hydrolase Isozyme L1 in Asymptomatic C9orf72 Hexanucleotide Repeat Expansion Carriers.

Elizabeth R Dellar, Iolanda Vendrell, Benazir Amein, David G Lester, Evan C Edmond, Katie Yoganathan, Thanuja Dharmadasa, Aitana Sogorb-Esteve, Roman Fischer, Kevin Talbot and 3 more

Abstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Annals of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Elizabeth R DellarNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.ORCID 0000-0002-8034-8511
Iolanda VendrellTarget Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Benazir AmeinNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
David G LesterNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Evan C EdmondNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Katie YoganathanNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Thanuja DharmadasaThe Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia.
Aitana Sogorb-EsteveDementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Roman FischerTarget Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Kevin TalbotNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Jonathan D RohrerDementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.ORCID 0000-0002-6155-8417
Martin R TurnerNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.ORCID 0000-0003-0267-3180
Alexander G ThompsonNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.ORCID 0000-0003-1063-3277

Funding

Chinese Academy of Medical Sciences Innovation Fund for Medical Science 2018-I2M-2-002Medical Research Council MR/T006927/1Medical Research Council MR/Y001095/1Motor Neurone Disease Association Lester/2450/795Motor Neurone Disease Association Thompson/Jan20/952-795
6 · The paper itself

Abstract

objectiveTo identify biochemical changes in individuals at higher risk of developing amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD) via C9orf72 hexanucleotide repeat expansion (HRE) heterozygosity.

methodsCross-sectional observational study of 48 asymptomatic C9orf72 HRE carriers, 39 asymptomatic non-carrier controls, 19 people with sporadic ALS, 10 with C9orf72 ALS, 14 with sporadic FTD, and 10 with C9orf72 FTD. Relative abundance of 30 pre-defined cerebrospinal fluid biomarkers of ALS and FTD were compared in asymptomatic C9orf72 HRE carriers and age-matched non-carrier controls. Differential abundance of these proteins was quantified using data independent acquisition mass spectrometry or electro chemiluminescent assay for neurofilament light chain. Unbiased analysis of the entire cerebrospinal fluid proteome was then carried out.

resultsUbiquitin carboxyl-hydrolase isozyme L1 levels were higher in asymptomatic C9orf72 HRE carriers compared with age-matched non-carriers (log

interpretationElevated cerebrospinal fluid ubiquitin carboxyl-hydrolase isozyme L1 levels in C9orf72 HRE carriers can occur in the absence of increased neurofilament levels, potentially reflecting either compensatory or pathogenic mechanisms preceding rapid neuronal loss. This brings forward the window on changes associated with the C9orf72 HRE carrier state, with potential to inform understanding of penetrance and approaches to prevention. ANN NEUROL 2025;97:449-459.

Indexed as

Amyotrophic Lateral SclerosisC9orf72 ProteinFrontotemporal DementiaAdultAgedBiomarkersCross-Sectional StudiesDNA Repeat ExpansionFemaleHeterozygoteHumansMaleMiddle AgedNeurofilament ProteinsBiomarkersC9orf72 ProteinC9orf72 protein, humanNeurofilament Proteins

Identifiers

PMID39548852
PMCPMC11831881

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.