ArticleNeurobiology of aging2020
Apolipoprotein E isoforms differentially regulate matrix metallopeptidase 9 function in Alzheimer's disease.
Article in Neurobiology of aging, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Impact of Apolipoprotein E4 on blood-brain barrier integrity in target replacement murine models: a systematic review and meta-analysis.Alzheimer's research & therapy · 2026Pooled it
- Matrix metalloproteinase-9 is associated with CX3CL1 on tau and amyloid biomarker pathways in APOE4 carriers.Neurobiology of disease · 2026Trial
- Review
- The Potential Use of Matrix Metalloproteinases in Alzheimer's Disease Therapy.Journal of clinical medicine · 2026Review
- Neuron-Derived Extracellular Vesicles: Emerging Regulators in Central Nervous System Disease Progression.Molecular neurobiology · 2025Review
- Aβ Deposition in Extracellular Space Disrupts Glial-Neuron Communication and Triggers Alzheimer's Disease.Aging and disease · 2025Review
- Understanding the role of microglia in Alzheimer's disease: insights into mechanisms, acupuncture, and potential therapeutic targets.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2025Review
- Blood-brain barrier disruption: a pervasive driver and mechanistic link between traumatic brain injury and Alzheimer's disease.Translational neurodegeneration · 2025Review
- The Link Between Matrix Metalloproteinases and Alzheimer's Disease Pathophysiology.Molecular neurobiology · 2025Review
- Andrographolide Improves ApoE4-Mediated Blood-Brain Barrier Injury by Alleviating Inflammation.Molecular neurobiology · 2024Article
- Novel Therapeutic Strategies in Alzheimer's Disease: Pitfalls and Challenges of Anti-Amyloid Therapies and Beyond.Journal of clinical medicine · 2024Review
- Matrix Remodeling Enzymes as Potential Fluid Biomarkers of Neurodegeneration in Alzheimer's Disease.International journal of molecular sciences · 2024Article
- Repetitive head trauma and apoE4 induce chronic cerebrovascular alterations that impair tau elimination from the brain.Experimental neurology · 2024Article
- Apolipoprotein ε in Brain and Retinal Neurodegenerative Diseases.Aging and disease · 2023Review
- Sex differences in Alzheimer's disease: plasma MMP-9 and markers of disease severity.Alzheimer's research & therapy · 2022Article
- Altered Balance of Reelin Proteolytic Fragments in the Cerebrospinal Fluid of Alzheimer's Disease Patients.International journal of molecular sciences · 2022Article
- Little genomic support for Cyclophilin A-matrix metalloproteinase-9 pathway as a therapeutic target for cognitive impairment in APOE4 carriers.Scientific reports · 2022Article
- Phosphorylated Tau 181 Serum Levels Predict Alzheimer's Disease in the Preclinical Stage.Frontiers in aging neuroscience · 2022Article
- MMP9 modulation improves specific neurobehavioral deficits in a mouse model of Alzheimer's disease.BMC neuroscience · 2021Article
- Structural Covariance Network as an Endophenotype in Alzheimer's Disease-Susceptible Single-Nucleotide Polymorphisms and the Correlations With Cognitive Outcomes.Frontiers in aging neuroscience · 2021Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Apolipoprotein E (APOE) has been shown to influence amyloid-β (Aβ) clearance from the brain in an isoform-specific manner. Our prior work showed that Aβ transit across the blood-brain-barrier was reduced by apoE4, compared to other apoE isoforms, due to elevated lipoprotein receptor shedding in brain endothelia. Recently, we demonstrated that matrix metallopeptidase 9 (MMP-9) induces lipoprotein receptor proteolysis in an apoE isoform-dependent manner, which impacts Aβ elimination from the brain. The current studies interrogated the relationship between apoE and MMP-9 and found that apoE impacted proMMP-9 cellular secretion from brain endothelia (apoE2 < apoE3 = apoE4). In a cell-free assay, apoE dose-dependently reduced MMP-9 activity, with apoE4 showing a significantly weaker ability to inhibit MMP-9 function than apoE2 or apoE3. Finally, we observed elevated MMP-9 expression and activity in the cerebrovasculature of both human and animal AD brain specimens with an APOE4 genotype. Collectively, these findings suggest a role for apoE in regulating MMP-9 disposition and may describe the effect of apoE4 on Aβ pathology in the AD brain.
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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.