ArticleThe Journal of experimental medicine2023
Age-related alterations in meningeal immunity drive impaired CNS lymphatic drainage.
Article in The Journal of experimental medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.
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
72 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Role of meningeal lymphatic vessels in brain homeostasis.Frontiers in immunology · 2025Pooled it
- Cerebrospinal fluid and dural accumulation of α-synuclein impairs CNS clearance in Parkinson's disease.The Journal of experimental medicine · 2026Article
- The effects of IFNγ on tissue physiology through structural cells.Nature reviews. Immunology · 2026Review
- Central nervous system lymphatic network: from the maintenance of brain homeostasis to emerging therapeutic perspectives in neurodegenerative diseases.Translational neurodegeneration · 2026Review
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- Article
- Meningeal lymphatic dysfunction in Alzheimer's disease: molecular mechanisms, clinical implications, and future perspectives.Molecular neurodegeneration · 2026Review
- Disrupted drainage in the aging brain: Meningeal lymphatic decline as a convergent axis of vulnerability.Neurobiology of aging · 2026Review
- Cardiomyocyte-Derived Apelin Rescues Viral Myocarditis-Induced Cardiac Lymphatic Dysfunction and Remodeling.JACC. Basic to translational science · 2026Article
- Reconstructing cerebral lymphatic clearance: an emerging target in the Alzheimer's disease therapeutic pipeline.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Therapeutic targeting of neuroimmune mechanisms in neurodegeneration.Nature reviews. Drug discovery · 2026Review
- Cardiovascular ageing: hallmarks, signaling pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Structural immunity: immune cells as architects of tissue barriers.Nature reviews. Immunology · 2026Review
- The Glymphatic System and Meningeal Lymphatics: Current Understandings and Future Perspectives.MedComm · 2026Review
- The meninges as a neuroimmune interface: structure, barriers and roles in CNS disease.Fluids and barriers of the CNS · 2026Review
- New Strategies for the Prevention and Therapy of Alzheimer's Disease Based on Stimulation of Brain Drainage and Lymphatic Clearance.International journal of molecular sciences · 2026Review
- Photoacoustic computed tomography monitors cerebrospinal fluid dynamics and glymphatic function.Nature communications · 2026Article
- Childhood brain tumors instruct cranial hematopoiesis and immunotolerance.Nature genetics · 2026Article
- The Aging Meninges: Anatomical and Immunological Remodeling as Emerging Diagnostic Biomarkers of Cerebral Senescence-A Narrative Review.Diagnostics (Basel, Switzerland) · 2026Review
- Barrier-Immune Gating Failure in Gut-Brain Neuroinflammation: A Working Hypothesis and Conceptual Framework.Behavioural neurology · 2026Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
The meningeal lymphatic network enables the drainage of cerebrospinal fluid (CSF) and facilitates the removal of central nervous system (CNS) waste. During aging and in Alzheimer's disease, impaired meningeal lymphatic drainage promotes the buildup of toxic misfolded proteins in the CNS. Reversing this age-related dysfunction represents a promising strategy to augment CNS waste clearance; however, the mechanisms underlying this decline remain elusive. Here, we demonstrate that age-related alterations in meningeal immunity underlie this lymphatic impairment. Single-cell RNA sequencing of meningeal lymphatic endothelial cells from aged mice revealed their response to IFNγ, which was increased in the aged meninges due to T cell accumulation. Chronic elevation of meningeal IFNγ in young mice via AAV-mediated overexpression attenuated CSF drainage-comparable to the deficits observed in aged mice. Therapeutically, IFNγ neutralization alleviated age-related impairments in meningeal lymphatic function. These data suggest manipulation of meningeal immunity as a viable approach to normalize CSF drainage and alleviate the neurological deficits associated with impaired waste removal.
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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.