ArticleAlzheimer's research & therapy2022
Loss of perivascular aquaporin-4 localization impairs glymphatic exchange and promotes amyloid β plaque formation in mice.
Article in Alzheimer's research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 154 papers, 1 of them a synthesis that pooled it.
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Who cites it
154 citing papers in PubMed, 1 synthesis or guideline pooled it, 213 citations in OpenAlex.
- Unveiling the glymphatic system's impact on neurodegenerative diseases: a comprehensive bibliometric analysis (2012-2024).Frontiers in aging neuroscience · 2025Pooled it
- The glymphatic system clears amyloid beta and tau from brain to plasma in humans.Nature communications · 2026Trial
- tDCS improves early Alzheimer's disease by synaptic vesicle fusion and release.Military Medical Research · 2026Article
- Article
- DTI-ALPS as a Biomarker of Small Vessel Disease Progression and Amyloid-β in Normal Aging: A 3-Year Longitudinal Study.Human brain mapping · 2026Article
- Spatial organization of AQP4 water channel expression in the human brain.Science advances · 2026Article
- Isolation of Brain Microglia to Study Persistence of Human Immunodeficiency Virus-1.Journal of visualized experiments : JoVE · 2026Article
- Temporal transcriptomic remodeling after controlled cortical impact reveals delayed AQP4/SNTA1 expression imbalance associated with ion-homeostatic remodeling.bioRxiv : the preprint server for biology · 2026Article
- Integrated Transcriptomic Analysis Reveals Coordinated Gliovascular Remodeling Across Diffuse Glioma Grades.Cancers · 2026Article
- Cerebral venous blood flow regulates intracerebral pressure and brain clearance via meningeal lymphatic vessels.Nature neuroscience · 2026Article
- Transcriptional risk score for chronic kidney disease: relation to Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Calcium dysregulation in neurovascular function in Alzheimer's disease: mechanisms, therapeutic targets.GeroScience · 2026Review
- Entorhinal Astrocyte Transplants Restore Spatial Exploration and Alleviate Amyloid-Beta Pathology in Alzheimer's Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cerebral Intramural Cells: A Missing Cellular Link Between Vascular Aging and Alzheimer's Disease.International journal of molecular sciences · 2026Review
- Glycation at the Gate: A Brain Endothelial Glycocalyx Model and Therapeutic Roadmap for Alzheimer's Disease.Biomedicines · 2026Article
- The Glial Autophagy-Lysosomal-Inflammation Axis in Alzheimer's Disease: a Unifying Mechanistic Framework.Molecular neurobiology · 2026Review
- Glymphatic Dysfunction in Children With Type 2 and 3 Spinal Muscular Atrophy.CNS neuroscience & therapeutics · 2026Article
- Regional astrocyte dysregulation and altered glymphatic-related markers in Alzheimer's disease frontal cortex.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Serial failure of the brain clearance continuum in Alzheimer's disease: mechanisms and therapeutic perspectives.Journal of neurology · 2026Review
- The Clearance-Centered Bottleneck in Alzheimer's Disease: From Coupled Glymphatic-Lymphatic Circuits to Therapeutic Opportunities.Molecular neurobiology · 2026Review
94 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundSlowed clearance of amyloid β (Aβ) is believed to underlie the development of Aβ plaques that characterize Alzheimer's disease (AD). Aβ is cleared in part by the glymphatic system, a brain-wide network of perivascular pathways that supports the exchange of cerebrospinal and brain interstitial fluid. Glymphatic clearance, or perivascular CSF-interstitial fluid exchange, is dependent on the astroglial water channel aquaporin-4 (AQP4) as deletion of Aqp4 in mice slows perivascular exchange, impairs Aβ clearance, and promotes Aβ plaque formation.
methodsTo define the role of AQP4 in human AD, we evaluated AQP4 expression and localization in a human post mortem case series. We then used the α-syntrophin (Snta1) knockout mouse model which lacks perivascular AQP4 localization to evaluate the effect that loss of perivascular AQP4 localization has on glymphatic CSF tracer distribution. Lastly, we crossed this line into a mouse model of amyloidosis (Tg2576 mice) to evaluate the effect of AQP4 localization on amyloid β levels.
resultsIn the post mortem case series, we observed that the perivascular localization of AQP4 is reduced in frontal cortical gray matter of subjects with AD compared to cognitively intact subjects. This decline in perivascular AQP4 localization was associated with increasing Aβ and neurofibrillary pathological burden, and with cognitive decline prior to dementia onset. In rodent studies, Snta1 gene deletion slowed CSF tracer influx and interstitial tracer efflux from the mouse brain and increased amyloid β levels.
conclusionsThese findings suggest that the loss of perivascular AQP4 localization may contribute to the development of AD pathology in human populations.
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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.