Observational studyNature medicine2025
Somatic CAG repeat expansion in blood associates with biomarkers of neurodegeneration in Huntington's disease decades before clinical motor diagnosis.
Abstract readObservational Study
In one paragraph
Observational study in Nature medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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38citing papers in PubMed, 1 pooled it
–field-weighted citation impact
What it found
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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.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Systematic Review with Meta-Analysis of Biofluid Markers for Huntington's Disease.Movement disorders : official journal of the Movement Disorder Society · 2025Pooled it
- Stage-dependent tau-PET signatures in Huntington's disease revealed by [¹⁸F]PI-2620.European journal of nuclear medicine and molecular imaging · 2026Article
- Fluid and Imaging Biomarkers in Huntington's Disease.Current neurology and neuroscience reports · 2026Review
- Decreased cerebrospinal fluid TNFRSF8 (sCD30) confirmed as a biomarker of Huntington's disease progression.Journal of neurology · 2026Article
- Targeting toxic HTT1a could be the key to treating Huntington disease.Nature reviews. Neurology · 2026Article
- Toward the clinical application of long-read sequencing in repeat-expansion disorders.Nature genetics · 2026Review
- Clinical implications of loss of interruption variants for diagnosis, genetic counselling, and clinical trials in Huntington's disease.Journal of Huntington's disease · 2026Review
- The countdown paradox: time-varying analysis of biomarker-clock age and symptom onset.medRxiv : the preprint server for health sciences · 2026Article
- The role of psychopharmacology and cognitive neuroscience in understanding the brain in the treatment of psychiatric disorders and neurological diseases for the benefit of society.Journal of psychopharmacology (Oxford, England) · 2026Article
- Pentanucleotide repeat instability and transmission in benign adult familial myoclonic epilepsy types 1, 4, and 8.Epilepsia · 2026Article
- A computational model for quantifying instability of tandem repeats across the genome.bioRxiv : the preprint server for biology · 2026Article
- Substantia Nigra as Brainstem Signature in Pediatric-Onset Huntington's Disease: The RAREST-JHD Study.Movement disorders clinical practice · 2026Article
- The Tale of the Guanosine Tract in Repeat Expansion Disorders.Molecular neurobiology · 2026Review
- Shake and bake: a robust and cost-effective proteomic sample preparation workflow for plasma and cerebrospinal fluid.Clinical proteomics · 2026Article
- Huntington's disease clinical trials update: October 2025.Journal of Huntington's disease · 2026Review
- Sequence Variants in Small CAG Repeat Expansions of theNeurology · 2026Article
- Epigenetic Dysregulation in Neurodegeneration: The Role of Histone Deacetylases and Emerging Inhibitor Strategies.Biomolecules · 2026Review
- Large scale functional and effective connectivity alterations cross the Huntington's disease integrated staging system.NeuroImage. Clinical · 2026Article
- Discovery of disrupted sustained attention and altered functional connectivity in far-from-onset Huntington's disease gene-expanded young adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Huntington disease: somatic expansion, pathobiology and therapeutics.Nature reviews. Neurology · 2026Review
Corrections and comments
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Authors and funding
33 authors.
Rachael I Scahill *Huntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Mena Farag *Huntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.ORCID http://orcid.org/0000-0002-0679-0117
Michael J MurphyHuntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Nicola Z HobbsHuntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Michela LeocadiHuntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Christelle LangleyDepartment of Psychiatry, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0001-5061-2820
Harry KnightsHuntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Marc CiosiSchool of Molecular Biosciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.ORCID http://orcid.org/0000-0002-7663-4080
Kate FayerHuntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Mitsuko NakajimaHuntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Olivia ThackerayHuntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Johan GobomDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.ORCID http://orcid.org/0000-0001-6193-6193
John RönnholmDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
Sophia WeinerDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.ORCID http://orcid.org/0009-0000-2298-220X
Yara R HassanHuntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Nehaa K P PonrajSchool of Molecular Biosciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.ORCID http://orcid.org/0009-0002-9576-5753
Carlos Estevez-FragaHuntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.ORCID http://orcid.org/0000-0001-6855-1093
Christopher S ParkerDepartment of Computer Science and Centre for Medical Image Computing, University College London, London, UK.
Ian B MaloneDementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Harpreet HyareDepartment of Brain Repair and Rehabilitation, UCL Queen Square Institute of Neurology, University College London, London, UK.
Jeffrey D LongDepartment of Psychiatry and Biostatistics, Carver College of Medicine and College of Public Health, University of Iowa, Iowa City, Iowa, USA.ORCID http://orcid.org/0000-0001-7181-9652
Amanda HeslegraveDementia Research Institute, University College London, London, UK.
Cristina SampaioFaculdade Medicina da Universidade de Lisboa (FMUL), Lisbon, Portugal.ORCID http://orcid.org/0000-0002-7052-9079
Hui ZhangDepartment of Computer Science and Centre for Medical Image Computing, University College London, London, UK.ORCID http://orcid.org/0000-0002-5426-2140
Trevor W RobbinsDepartment of Psychology, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0003-0642-5977
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
Edward J WildHuntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.ORCID http://orcid.org/0000-0002-6921-7887
Geraint ReesUCL Institute of Cognitive Neuroscience, University College London, London, UK.ORCID http://orcid.org/0000-0002-9623-7007
James B RoweDepartment of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.ORCID http://orcid.org/0000-0001-7216-8679
Barbara J SahakianDepartment of Psychiatry, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0001-7352-1745
Darren G MoncktonSchool of Molecular Biosciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.ORCID http://orcid.org/0000-0002-8298-8264
Douglas R LangbehnDepartment of Psychiatry and Biostatistics, Carver College of Medicine and College of Public Health, University of Iowa, Iowa City, Iowa, USA.
Sarah J TabriziHuntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK. s.tabrizi@ucl.ac.uk.ORCID http://orcid.org/0000-0003-2716-2045
Funding
Medical Research Council MC_UU_00030/14Wellcome TrustWellcome Trust (Wellcome) 223082/Z/21/Z
Abstract
Huntington's disease (HD) is an autosomal dominant neurodegenerative disease with the age at which characteristic symptoms manifest strongly influenced by inherited HTT CAG length. Somatic CAG expansion occurs throughout life and understanding the impact of somatic expansion on neurodegeneration is key to developing therapeutic targets. In 57 HD gene expanded (HDGE) individuals, ~23 years before their predicted clinical motor diagnosis, no significant decline in clinical, cognitive or neuropsychiatric function was observed over 4.5 years compared with 46 controls (false discovery rate (FDR) > 0.3). However, cerebrospinal fluid (CSF) markers showed very early signs of neurodegeneration in HDGE with elevated neurofilament light (NfL) protein, an indicator of neuroaxonal damage (FDR = 3.2 × 10
Indexed as
Huntingtin ProteinHuntington DiseaseTrinucleotide Repeat ExpansionAdultAgedBiomarkersEnkephalinsFemaleHumansMaleMiddle AgedNeurofilament ProteinsProtein PrecursorsBiomarkersEnkephalinsHTT protein, humanHuntingtin Proteinneurofilament protein LNeurofilament ProteinsProtein Precursors
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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.