Evidence map›Paper›PMID 33219289›Full record

ArticleScientific reports2020

Disease-related Huntingtin seeding activities in cerebrospinal fluids of Huntington's disease patients.

C Y Daniel Lee, Nan Wang, Koning Shen, Matthew Stricos, Peter Langfelder, Kristina H Cheon, Etty P Cortés, Harry V Vinters, Jean Paul Vonsattel, Nancy S Wexler and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

  1. DNAJB6: A guardian against neurodegeneration.Neural regeneration research · 2026
    Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Review
  11. Non-Cell Autonomous and Epigenetic Mechanisms of Huntington's Disease.International journal of molecular sciences · 2021
    Review
  12. Article
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.

C Y Daniel LeeCenter for Neurobehavioral Genetics, The Jane and Terry Semel Institute for Neuroscience & Human Behavior, University of California, Los Angeles, Los Angeles, USA.
Nan WangCenter for Neurobehavioral Genetics, The Jane and Terry Semel Institute for Neuroscience & Human Behavior, University of California, Los Angeles, Los Angeles, USA.
Koning ShenDepartment of Biology and BioX Program, Stanford University, Stanford, CA, USA.
Matthew StricosCenter for Neurobehavioral Genetics, The Jane and Terry Semel Institute for Neuroscience & Human Behavior, University of California, Los Angeles, Los Angeles, USA.
Peter LangfelderCenter for Neurobehavioral Genetics, The Jane and Terry Semel Institute for Neuroscience & Human Behavior, University of California, Los Angeles, Los Angeles, USA.
Kristina H CheonCenter for Neurobehavioral Genetics, The Jane and Terry Semel Institute for Neuroscience & Human Behavior, University of California, Los Angeles, Los Angeles, USA.
Etty P CortésDivision of Aging and Dementia, Department of Neurology, Columbia University Medical Center, New York, NY, USA.
Harry V VintersDepartment of Pathology and Laboratory Medicine, Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Jean Paul VonsattelDivision of Aging and Dementia, Department of Neurology, Columbia University Medical Center, New York, NY, USA.
Nancy S WexlerDepartments of Neurology and Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Robert DamoiseauxCalifornia NanoSystems Institute, University of California, Los Angeles, CA, USA.
Judith FrydmanDepartment of Biology and BioX Program, Stanford University, Stanford, CA, USA.
X William YangCenter for Neurobehavioral Genetics, The Jane and Terry Semel Institute for Neuroscience & Human Behavior, University of California, Los Angeles, Los Angeles, USA. xwyang@mednet.ucla.edu.

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8M
NINDS Biomarker RepositoryU24NS095871 · NINDS · INDIANA UNIVERSITY INDIANAPOLIS · PI TATIANA M. FOROUD · 2015 to 2026
$18.3M
Integrative Center for Neurogenetics and Neurogenomics - OverallP30NS062691 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI COPPOLA, GIOVANNI · 2009 to 2018
$7.4M
BAC Transgenic Mouse Models of TREM2 to Study Neuroprotective Mechanisms in ADRF1AG056114 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YANG, XIANGDONG WILLIAM · 2017 to 2017
$4.1M
Novel mouse genetic models to study modifiers of Huntington’s diseaseR01NS113612 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YANG, XIANGDONG WILLIAM · 2019 to 2023
$3.2M
Novel Genetic Strategy for Sparse Labeling and Manipulation of Mammalian NeuronsU01MH106008 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YANG, XIANGDONG WILLIAM · 2014 to 2016
$2.0M
Complement-Microglia Interaction in Synaptic Loss and Neurodegeneration in HDR01NS084298 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI STEVENS, BETH ANN, YANG, XIANGDONG WILLIAM · 2014 to 2018
$1.8M
Validating NT17 Dependent Mechanisms in Huntington's Disease SuppressionR01NS074312 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YANG, XIANGDONG WILLIAM · 2011 to 2014
$1.4M
NCI NIH HHS P30 CA016042NIA NIH HHS RF1 AG056114NIA NIH HHS U24 AG021886NIMH NIH HHS U01 MH106008NINDS NIH HHS P30 NS062691NINDS NIH HHS R01 NS074312NINDS NIH HHS R01 NS084298NINDS NIH HHS R01 NS113612NINDS NIH HHS U24 NS095871
6 · The paper itself

Abstract

In Huntington's disease (HD), the mutant Huntingtin (mHTT) is postulated to mediate template-based aggregation that can propagate across cells. It has been difficult to quantitatively detect such pathological seeding activities in patient biosamples, e.g. cerebrospinal fluids (CSF), and study their correlation with the disease manifestation. Here we developed a cell line expressing a domain-engineered mHTT-exon 1 reporter, which showed remarkably high sensitivity and specificity in detecting mHTT seeding species in HD patient biosamples. We showed that the seeding-competent mHTT species in HD CSF are significantly elevated upon disease onset and with the progression of neuropathological grades. Mechanistically, we showed that mHTT seeding activities in patient CSF could be ameliorated by the overexpression of chaperone DNAJB6 and by antibodies against the polyproline domain of mHTT. Together, our study developed a selective and scalable cell-based tool to investigate mHTT seeding activities in HD CSF, and demonstrated that the CSF mHTT seeding species are significantly associated with certain disease states. This seeding activity can be ameliorated by targeting specific domain or proteostatic pathway of mHTT, providing novel insights into such pathological activities.

Indexed as

AdultAgedAged, 80 and overBrainCell LineCerebrospinal FluidExonsFemaleGenes, ReporterHSP40 Heat-Shock ProteinsHumansHuntingtin ProteinHuntington DiseaseIntravital MicroscopyMaleMiddle AgedDNAJB6 protein, humanHSP40 Heat-Shock ProteinsHTT protein, humanHuntingtin ProteinMolecular ChaperonesNerve Tissue Proteins

Identifiers

PMID33219289
PMCPMC7679413

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Registered trials

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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.