ArticleThe Journal of experimental medicine2022
Glymphatic system clears extracellular tau and protects from tau aggregation and neurodegeneration.
Article in The Journal of experimental medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 175 papers, 3 of them syntheses that pooled it.
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The trial behind it
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Who cites it
175 citing papers in PubMed, 3 syntheses or guidelines pooled it, 242 citations in OpenAlex.
- Unveiling the glymphatic system's impact on neurodegenerative diseases: a comprehensive bibliometric analysis (2012-2024).Frontiers in aging neuroscience · 2025Pooled it
- Role of meningeal lymphatic vessels in brain homeostasis.Frontiers in immunology · 2025Pooled it
- Meta-analysis of the relationship between the number and location of perivascular spaces in the brain and cognitive function.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Pooled it
- The glymphatic system clears amyloid beta and tau from brain to plasma in humans.Nature communications · 2026Trial
- Article
- Spatial organization of AQP4 water channel expression in the human brain.Science advances · 2026Article
- Central nervous system lymphatic network: from the maintenance of brain homeostasis to emerging therapeutic perspectives in neurodegenerative diseases.Translational neurodegeneration · 2026Review
- Novel Therapeutic Insights Into Alzheimer's Disease: Glymphatic System and Meningeal Lymphatic Vessels.Aging cell · 2026Review
- Shared genetic architecture between DTI-ALPS traits and neurodegenerative diseases.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Sleep Disorders in Neurodegenerative Diseases: Pathological Correlations and Underlying Mechanisms.Neuroscience bulletin · 2026Review
- Voluntary Exercise and Hippocampal Memory Enhancement: Decoding the Molecular Blueprint.Journal of molecular neuroscience : MN · 2026Review
- The Glial Autophagy-Lysosomal-Inflammation Axis in Alzheimer's Disease: a Unifying Mechanistic Framework.Molecular neurobiology · 2026Review
- Dorsal raphe tau pathology disrupts sleep-wake orchestration and sleep architecture in a sex-specific manner.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Lung endothelial cytopathic tau is sufficient to impair long-term potentiation during infection.American journal of respiratory cell and molecular biology · 2026Article
- The Clearance-Centered Bottleneck in Alzheimer's Disease: From Coupled Glymphatic-Lymphatic Circuits to Therapeutic Opportunities.Molecular neurobiology · 2026Review
- AQP4-dependent enhancement of glymphatic function attenuates tau pathology and neurodegeneration in PS19 mice.Molecular neurodegeneration · 2026Article
- Aquaporin-4 mislocalization from astrocyte endfeet prolongs survival in a prion-cerebral amyloid angiopathy model.bioRxiv : the preprint server for biology · 2026Article
- Anatomical determinants of DTI-ALPS: effects of ROI definition, ventricular morphology, and periventricular deformation.bioRxiv : the preprint server for biology · 2026Article
- Omega-3 Fatty Acids and Alzheimer's Disease: Toward a New Understanding of Neuroprotective Mechanisms and Intervention Strategies.Marine drugs · 2026Review
- Meningeal lymphatic dysfunction in Alzheimer's disease: molecular mechanisms, clinical implications, and future perspectives.Molecular neurodegeneration · 2026Review
115 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulation of tau has been implicated in various neurodegenerative diseases termed tauopathies. Tau is a microtubule-associated protein but is also actively released into the extracellular fluids including brain interstitial fluid and cerebrospinal fluid (CSF). However, it remains elusive whether clearance of extracellular tau impacts tau-associated neurodegeneration. Here, we show that aquaporin-4 (AQP4), a major driver of the glymphatic clearance system, facilitates the elimination of extracellular tau from the brain to CSF and subsequently to deep cervical lymph nodes. Strikingly, deletion of AQP4 not only elevated tau in CSF but also markedly exacerbated phosphorylated tau deposition and the associated neurodegeneration in the brains of transgenic mice expressing P301S mutant tau. The current study identified the clearance pathway of extracellular tau in the central nervous system, suggesting that glymphatic clearance of extracellular tau is a novel regulatory mechanism whose impairment contributes to tau aggregation and neurodegeneration.
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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.