ArticleThe Journal of clinical investigation2015
Quantification of mutant huntingtin protein in cerebrospinal fluid from Huntington's disease patients.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers, 1 of them a synthesis that pooled it.
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Who cites it
145 citing papers in PubMed, 1 synthesis or guideline pooled it, 259 citations in OpenAlex.
- Systematic Review with Meta-Analysis of Biofluid Markers for Huntington's Disease.Movement disorders : official journal of the Movement Disorder Society · 2025Pooled it
- An alternative splicing modulator decreases mutant HTT and improves the molecular fingerprint in Huntington's disease patient neurons.Nature communications · 2022Trial
- Decreased cerebrospinal fluid TNFRSF8 (sCD30) confirmed as a biomarker of Huntington's disease progression.Journal of neurology · 2026Article
- A machine learning-derived speech index as a biomarker for Huntington's disease severity.Journal of neurology · 2026Article
- Electrochemical Detection of Neuronal Injury in Cell Culture Samples: A Cost-Effective Biosensor for Neurofilament Light Sensing.Biosensors · 2026Article
- Gene therapy for huntington's disease: advances, challenges, and future perspectives.Neurogenetics · 2026Review
- Eye manifestations in Huntington's disease: an update on the potential of ocular biomarkers.Journal of neurology · 2026Review
- Cerebrospinal Fluid Proenkephalin Predicts Striatal Atrophy Decades before Clinical Motor Diagnosis in Huntington's Disease.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Enhancing the detection of HTT1a with neoepitope antibodies in mouse models of Huntington's disease.Brain communications · 2026Article
- Extracellular vesicle-based therapies for neurodegenerative diseases.NeuroImmune pharmacology and therapeutics · 2025Review
- Exploring the skin as an open window onto neurodegenerative diseases.Translational neurodegeneration · 2025Review
- PET imaging with [¹¹C]CHDI-00485180-R, designed as radioligand for aggregated mutant huntingtin, in people with Huntington's disease.European journal of nuclear medicine and molecular imaging · 2025Article
- Accurate Quantification of Mutant and Wild-Type polyQ Proteins Using Simple Western Capillary Immunoassays.Molecular neurobiology · 2025Article
- The Role of MicroRNAs in Neurodegeneration: Insights from Huntington's Disease.Molecular neurobiology · 2025Review
- Challenges and advances for huntingtin detection in cerebrospinal fluid: in support of relative quantification.Biomarker research · 2025Article
- Inhibitor-based modulation of huntingtin aggregation mechanisms mitigates fibril-induced cellular stress.Nature communications · 2025Article
- The therapeutic potential of (R)-carvedilol in Huntington's disease through enhancement of autophagy-lysosomal pathway via GSK-3β inhibition.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Somatic CAG repeat expansion in blood associates with biomarkers of neurodegeneration in Huntington's disease decades before clinical motor diagnosis.Nature medicine · 2025Observational
- Advances in Huntington's Disease Biomarkers: A 10-Year Bibliometric Analysis and a Comprehensive Review.Biology · 2025Review
- Neural Networks of Knowledge: Ontologies Pioneering Precision Medicine in Neurodegenerative Diseases.Current neuropharmacology · 2025Review
85 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundQuantification of disease-associated proteins in the cerebrospinal fluid (CSF) has been critical for the study and treatment of several neurodegenerative disorders; however, mutant huntingtin protein (mHTT), the cause of Huntington's disease (HD), is at very low levels in CSF and, to our knowledge, has never been measured previously.
methodsWe developed an ultrasensitive single-molecule counting (SMC) mHTT immunoassay that was used to quantify mHTT levels in CSF samples from individuals bearing the HD mutation and from control individuals in 2 independent cohorts.
resultsThis SMC mHTT immunoassay demonstrated high specificity for mHTT, high sensitivity with a femtomolar detection threshold, and a broad dynamic range. Analysis of the CSF samples showed that mHTT was undetectable in CSF from all controls but quantifiable in nearly all mutation carriers. The mHTT concentration in CSF was approximately 3-fold higher in patients with manifest HD than in premanifest mutation carriers. Moreover, mHTT levels increased as the disease progressed and were associated with 5-year onset probability. The mHTT concentration independently predicted cognitive and motor dysfunction. Furthermore, the level of mHTT was associated with the concentrations of tau and neurofilament light chain in the CSF, suggesting a neuronal origin for the detected mHTT.
conclusionsWe have demonstrated that mHTT can be quantified in CSF from HD patients using the described SMC mHTT immunoassay. Moreover, the level of mHTT detected is associated with proximity to disease onset and diminished cognitive and motor function. The ability to quantify CSF mHTT will facilitate the study of HD, and mHTT quantification could potentially serve as a biomarker for the development and testing of experimental mHTT-lowering therapies for HD.
trial registrationNot applicable.
fundingCHDI Foundation Inc.; Medical Research Council (MRC) UK; National Institutes for Health Research (NIHR); Rosetrees Trust; Swedish Research Council; and Knut and Alice Wallenberg Foundation.
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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.