Evidence mapPaperPMID 39226105Full record

ArticleJCI insight2024

Glymphatic influx and clearance are perturbed in Huntington's disease.

Hongshuai Liu, Lin Chen, Chuangchuang Zhang, Chang Liu, Yuguo Li, Liam Cheng, Yuxiao Ouyang, Catherine Rutledge, John Anderson, Zhiliang Wei and 6 more

Abstract read
In one paragraph

Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

14 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. The glymphatic system in Huntington's disease.Journal of Huntington's disease · 2025
    Review
  9. Review
  10. Review
  11. Diffusion along Perivascular Spaces as a Marker for Glymphatic System Impairment in Huntington's Disease.Movement disorders : official journal of the Movement Disorder Society · 2025
    Article
  12. Article
  13. Review
  14. 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

16 authors.

Hongshuai LiuDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Lin ChenF.M. Kirby Research Center, Kennedy Krieger Research Institute, Baltimore, USA.
Chuangchuang ZhangDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Chang LiuDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Yuguo LiF.M. Kirby Research Center, Kennedy Krieger Research Institute, Baltimore, USA.
Liam ChengDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Yuxiao OuyangDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Catherine RutledgeDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
John AndersonDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Zhiliang WeiRussell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Ziqin ZhangF.M. Kirby Research Center, Kennedy Krieger Research Institute, Baltimore, USA.
Hanzhang LuF.M. Kirby Research Center, Kennedy Krieger Research Institute, Baltimore, USA.
Peter Cm van ZijlF.M. Kirby Research Center, Kennedy Krieger Research Institute, Baltimore, USA.
Jeffrey J IliffVeterans Integrated Service Network (VISN) 20 Northwest Mental Illness Research, Education, and Clinical Center (MIRECC), VA Puget Sound Health Care System, Seattle, Washington, USA.
Jiadi XuF.M. Kirby Research Center, Kennedy Krieger Research Institute, Baltimore, USA.
Wenzhen DuanDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Funding

Cerebrospinal fluid exchange in Alzheimer's disease characterized by advanced MRI techniquesR01AG080104 · NIA · HUGO W. MOSER RES INST KENNEDY KRIEGER · 2024 to 2025
$1.4M
Advanced MRI biomarkers in HD mouse models translatable to humans: nature history and response to therapeuticsR01NS124084 · JOHNS HOPKINS UNIVERSITY · 2025 to 2025
$628k
Emerging role of glymphatic clearance in Huntington's diseaseR01NS127344 · JOHNS HOPKINS UNIVERSITY · 2025 to 2025
$455k
NHLBI NIH HHS R01 HL149742NIA NIH HHS R01 AG080104NINDS NIH HHS R01 NS082338NINDS NIH HHS R01 NS124084NINDS NIH HHS R01 NS127344NINDS NIH HHS R21 NS118079NINDS NIH HHS R21 NS135139NINDS NIH HHS R56 NS124084
6 · The paper itself

Abstract

The accumulation of mutant huntingtin protein aggregates in neurons is a pathological hallmark of Huntington's disease (HD). The glymphatic system, a brain-wide perivascular network, facilitates the exchange of interstitial fluid and cerebrospinal fluid (CSF), supporting interstitial solute clearance of brain wastes. In this study, we employed dynamic glucose-enhanced (DGE) MRI to measure d-glucose clearance from CSF as a tool to predict glymphatic function in a mouse model of HD. We found significantly diminished CSF clearance efficiency in HD mice before phenotypic onset. The impairment of CSF clearance efficiency worsened with disease progression. These DGE MRI findings in compromised glymphatic function were further verified with fluorescence-based imaging of CSF tracer influx, suggesting an impaired glymphatic function in premanifest HD. Moreover, expression of the astroglial water channel aquaporin-4 in the perivascular compartment, a key mediator of glymphatic function, was significantly diminished in both HD mouse brain and human HD brain. Our data, acquired using a clinically translatable MRI, indicate a perturbed glymphatic network in the HD brain. Further validation of these findings in clinical studies will provide insights into the potential of glymphatic clearance as a therapeutic target as well as an early biomarker in HD.

Indexed as

Aquaporin 4BrainDisease Models, AnimalGlymphatic SystemHuntington DiseaseMagnetic Resonance ImagingAnimalsCerebrospinal FluidFemaleGlucoseHumansHuntingtin ProteinMaleMiceMice, TransgenicMiddle AgedAqp4 protein, mouseAquaporin 4GlucoseHuntingtin ProteinNeurodegenerationNeuroimagingNeuroscience

Identifiers

PMID39226105
PMCPMC11530125

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.