ArticleJournal of Alzheimer's disease : JAD2019
Impaired Peripheral Lymphatic Function and Cerebrospinal Fluid Outflow in a Mouse Model of Alzheimer's Disease.
Article in Journal of Alzheimer's disease : JAD, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Intrathecal drug delivery in the era of nanomedicine.Advanced drug delivery reviews · 2020Pooled it
- Meningeal lymphatic dysfunction in Alzheimer's disease: molecular mechanisms, clinical implications, and future perspectives.Molecular neurodegeneration · 2026Review
- [Research progress on vascular endothelial growth factor C in meningeal lymphatic vessel-mediated clearance of amyloid β-protein].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Review
- Photoacoustic computed tomography monitors cerebrospinal fluid dynamics and glymphatic function.Nature communications · 2026Article
- Exploratory assessment of cerebrospinal fluid-related microdynamics after mild traumatic brain injury using intravoxel incoherent motion magnetic resonance imaging.Frontiers in neuroscience · 2026Article
- Neuroinflammation in Alzheimer disease.Nature reviews. Immunology · 2025Review
- Engineered 3D human neurovascular model of Alzheimer's disease to study vascular dysfunction.Biomaterials · 2025Article
- T Cells Trafficking into the Brain in Aging and Alzheimer's Disease.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Review
- Meningeal Lymphatics in Central Nervous System Diseases.Annual review of neuroscience · 2024Review
- Connecting the Dots: The Cerebral Lymphatic System as a Bridge Between the Central Nervous System and Peripheral System in Health and Disease.Aging and disease · 2024Review
- The nasal lymphatic route of CSF outflow: implications for neurodegenerative disease diagnosis and monitoring.Animal cells and systems · 2024Review
- Imaging peripheral lymphatic dysfunction in chronic conditions.Frontiers in physiology · 2023Review
- Blood Vessels as a Key Mediator for Ethanol Toxicity: Implication for Neuronal Damage.Life (Basel, Switzerland) · 2022Review
- The role of the meningeal lymphatic system in local meningeal inflammation and trigeminal nociception.Scientific reports · 2022Article
- Arachnoid membrane as a source of sphingosine-1-phosphate that regulates mouse middle cerebral artery tone.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
- Inflammatory Cascade in Alzheimer's Disease Pathogenesis: A Review of Experimental Findings.Cells · 2021Review
- CNS-Draining Meningeal Lymphatic Vasculature: Roles, Conundrums and Future Challenges.Frontiers in pharmacology · 2021Review
- Cerebral blood flow decrease as an early pathological mechanism in Alzheimer's disease.Acta neuropathologica · 2020Review
- The Development and Treatment of Lymphatic Dysfunction in Cancer Patients and Survivors.Cancers · 2020Review
- Assessing lymphatic route of CSF outflow and peripheral lymphatic contractile activity during head-down tilt using near-infrared fluorescence imaging.Physiological reports · 2020Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Cerebrospinal fluid (CSF) outflow from the brain occurs through absorption into the arachnoid villi and, more predominantly, through meningeal and olfactory lymphatics that ultimately drain into the peripheral lymphatics. Impaired CSF outflow has been postulated as a contributing mechanism in Alzheimer's disease (AD). Herein we conducted near-infrared fluorescence imaging of CSF outflow into the peripheral lymph nodes (LNs) and of peripheral lymphatic function in a transgenic mouse model of AD (5XFAD) and wild-type (WT) littermates. CSF outflow was assessed from change in fluorescence intensity in the submandibular LNs as a function of time following bolus, an intrathecal injection of indocyanine green (ICG). Peripheral lymphatic function was measured by assessing lymphangion contractile function in lymphatics draining into the popliteal LN following intradermal ICG injection in the dorsal aspect of the hind paw. The results show 1) significantly impaired CSF outflow into the submandibular LNs of 5XFAD mice and 2) reduced contractile frequency in the peripheral lymphatics as compared to WT mice. Impaired CSF clearance was also evidenced by reduction of fluorescence on ventral surfaces of extracted brains of 5XFAD mice at euthanasia. These results support the hypothesis that lymphatic congestion caused by reduced peripheral lymphatic function could limit CSF outflow and may contribute to the cause and/or progression of AD.
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Registered trials
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.