ArticlePsychopharmacology2017
Mechanism of depression as a risk factor in the development of Alzheimer's disease: the function of AQP4 and the glymphatic system.
Article in Psychopharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 1 of them a synthesis that pooled it.
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Who cites it
90 citing papers in PubMed, 1 synthesis or guideline pooled it, 148 citations in OpenAlex.
- The Association Between Antidepressant Effect of SSRIs and Astrocytes: Conceptual Overview and Meta-analysis of the Literature.Neurochemical research · 2021Pooled it
- Vortioxetine Improves Brain Glymphatic System Function, Functional Connectivity, and Cognitive Functions in Major Depressive Disorder.Depression and anxiety · 2025Trial
- The glymphatic system in sleep: a nexus of waste clearance, brain homeostasis, and disease intervention.Molecular psychiatry · 2026Review
- Modulation of depression through the neurobiological underpinnings of the glymphatic-rumination relationship.Psychological medicine · 2026Article
- Glymphatic dysfunction: a unifying hypothesis for delirium.Nature reviews. Neurology · 2026Review
- Glymphatic Dysfunction and Related Brain Structure Changes in Major Depressive Disorder: Effects of Glymphatic Function in Mediating Neuroinflammation.Psychiatry investigation · 2026Article
- Does Enriched Environment Improve Chronic Immobilization Stress-Induced Cognitive and Behavioral Changes in Adult Male Rats?Cellular and molecular neurobiology · 2026Article
- Adenosine AJournal of neurochemistry · 2026Article
- Cerebellar astrocytic alterations in depression.Translational psychiatry · 2026Article
- Role of glymphatic system function in cognitive dysfunction among patients with bipolar disorder.The international journal of neuropsychopharmacology · 2026Article
- Aquaporin-4 Dysfunction in Depression: From Pathogenic Mechanisms to Novel Therapeutic Targeting.International journal of molecular sciences · 2026Review
- Astrocytic KFrontiers in aging neuroscience · 2026Review
- Propranolol improves cognitive function and glymphatic system recovery through STAT3/MMP2 pathway after TBI.PloS one · 2026Article
- Article
- Nutritional Modulation of Impaired Blood-Brain Barrier Integrity and Function in Major Depression.International journal of molecular sciences · 2025Review
- CSF transport at the brain-meningeal border: effects on neurological health and disease.The Lancet. Neurology · 2025Review
- Local genetic covariance analysis with lipid traits identifies novel loci for early-onset Alzheimer's Disease.PLoS genetics · 2025Article
- Dihydroergotamine and Bromocriptine: Potential Drugs for the Treatment of Major Depressive Disorder and Alzheimer's Disease Comorbidity.Molecular neurobiology · 2025Article
- Assessing glymphatic-associated fluid dynamics in psychiatric disorders: evidence from neuroimaging - a review.Psychoradiology · 2025Review
- Evolutionary changes leading to efficient glymphatic circulation in the mammalian brain.Nature communications · 2024Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMany studies have indicated that a history of depression increases the risk of developing Alzheimer's disease (AD); however, the potential pathogenestic mechanism by which depression functions as a high risk factor for AD remains unknown. Recently, a "cerebral lymphatic system" referred to as "glymphatic system" has been demonstrated to be responsible for neuronal extracellular waste protein clearance via a paravascular pathway. However, the function of glymphatic pathway has not been determined in depressive disorders.
methodsThe present study used an animal model of chronic unpredictable mild stress (CUMS) to determine the function of glymphatic pathway by using fluorescence tracers. Immunohistochemistry was used to assess the accumulation of endogenous mouse and exogenous human amyloid beta 42 (Aβ42) in CUMS-treated mice with or without treatment with antidepressant fluoxetine.
findingsGlymphatic pathway circulation was impaired in mice treated with CUMS; moreover, glymphatic pathway dysfunction suppressed Aβ42 metabolism, because the accumulation of endogenous and exogenous Aβ42 was increased in the brains of the CUMS-treated mice. However, treatment with fluoxetine reversed these destructive effects of CUMS on glymphatic system. In anhedonic mice, the expression of the water channel aquaporin 4 (AQP4), a factor in glymphatic pathway dysfunction, was down-regulated in cortex and hippocampus.
conclusionThe dysfunction of glymphatic system suggested why a history of depression may be a strong risk factor for AD in anhedonic mice. We hope our study will contribute to an understanding of the risk mechanism of depressive disorder in the development of AD and the mechanisms of antidepressant therapies in AD.
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