ArticleMolecular neurodegeneration2016
Glymphatic distribution of CSF-derived apoE into brain is isoform specific and suppressed during sleep deprivation.
Article in Molecular neurodegeneration, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT03410095 (The Brain Changes in Sleep Apnea Study), which is not on this map. Cited by 145 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.
The Brain Changes in Sleep Apnea Study
Who cites it
145 citing papers in PubMed, 1 synthesis or guideline pooled it, 240 citations in OpenAlex.
- Pooled it
- A Quantitative Assessment of MRI-Visible Perivascular-Space Burden Across the Cognitive Spectrum: Associations with APOE ε4 Status and Venous Sinus Volume.Diagnostics (Basel, Switzerland) · 2026Article
- Serial failure of the brain clearance continuum in Alzheimer's disease: mechanisms and therapeutic perspectives.Journal of neurology · 2026Review
- The glymphatic system in sleep: a nexus of waste clearance, brain homeostasis, and disease intervention.Molecular psychiatry · 2026Review
- Diffusion Tensor Imaging Along the Perivascular Space in Veterans with Remote Mild Traumatic Brain Injuries.Journal of neurotrauma · 2026Article
- Enhanced Taylor-Aris dispersion in slender pulsatile annular channels: Implications for perivascular solute transport.Journal of fluid mechanics · 2026Article
- Perivascular spread of CSF-derived α-synuclein oligomers drives region-specific Parkinson's-like pathology.NPJ Parkinson's disease · 2026Article
- The choroid plexus- cerebrospinal fluid axis as a lifespan regulator of neural stem cells and circuit plasticity.Frontiers in neural circuits · 2026Review
- Glymphatic-meningeal lymphatic system imbalance: a peripheral-to-central inflammatory bridge in perioperative neurocognitive disorders.Frontiers in immunology · 2026Review
- ApoE expression across the CNS: Who, What, Where, When, and How (much)?Molecular neurodegeneration advances · 2026Review
- Shared Neuroinflammatory Mechanisms Across Dementia Types: An Integrative Review.International journal of molecular sciences · 2025Review
- Article
- Deciphering the role of APOE in cerebral amyloid angiopathy: from genetic insights to therapeutic horizons.Annals of medicine · 2025Review
- Sleep is a therapeutic window for photostimulation of drainage of aging brain.Frontiers of optoelectronics · 2025Article
- Mechanisms of high-density lipoprotein in regulating blood-brain barrier function: insights and implications.Fluids and barriers of the CNS · 2025Review
- Sleep deprivation and risk for Parkinson's disease: evidence and therapeutic implications.Journal of neurology · 2025Review
- Glymphatic and meningeal lymphatic dysfunction in Alzheimer's disease: Mechanisms and therapeutic perspectives.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Vascular Dementia: From Pathophysiology to Therapeutic Frontiers.Journal of clinical medicine · 2025Review
- Assessing morphological changes in the choroid plexus between standing and supine positions using a rotatable MRI system.Scientific reports · 2025Article
- Meningeal lymphatic drainage: novel insights into central nervous system disease.Signal transduction and targeted therapy · 2025Review
85 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundApolipoprotein E (apoE) is a major carrier of cholesterol and essential for synaptic plasticity. In brain, it's expressed by many cells but highly expressed by the choroid plexus and the predominant apolipoprotein in cerebrospinal fluid (CSF). The role of apoE in the CSF is unclear. Recently, the glymphatic system was described as a clearance system whereby CSF and ISF (interstitial fluid) is exchanged via the peri-arterial space and convective flow of ISF clearance is mediated by aquaporin 4 (AQP4), a water channel. We reasoned that this system also serves to distribute essential molecules in CSF into brain. The aim was to establish whether apoE in CSF, secreted by the choroid plexus, is distributed into brain, and whether this distribution pattern was altered by sleep deprivation.
methodsWe used fluorescently labeled lipidated apoE isoforms, lenti-apoE3 delivered to the choroid plexus, immunohistochemistry to map apoE brain distribution, immunolabeled cells and proteins in brain, Western blot analysis and ELISA to determine apoE levels and radiolabeled molecules to quantify CSF inflow into brain and brain clearance in mice. Data were statistically analyzed using ANOVA or Student's t- test.
resultsWe show that the glymphatic fluid transporting system contributes to the delivery of choroid plexus/CSF-derived human apoE to neurons. CSF-delivered human apoE entered brain via the perivascular space of penetrating arteries and flows radially around arteries, but not veins, in an isoform specific manner (apoE2 > apoE3 > apoE4). Flow of apoE around arteries was facilitated by AQP4, a characteristic feature of the glymphatic system. ApoE3, delivered by lentivirus to the choroid plexus and ependymal layer but not to the parenchymal cells, was present in the CSF, penetrating arteries and neurons. The inflow of CSF, which contains apoE, into brain and its clearance from the interstitium were severely suppressed by sleep deprivation compared to the sleep state.
conclusionsThus, choroid plexus/CSF provides an additional source of apoE and the glymphatic fluid transporting system delivers it to brain via the periarterial space. By implication, failure in this essential physiological role of the glymphatic fluid flow and ISF clearance may also contribute to apoE isoform-specific disorders in the long term.
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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.