ArticleBrain : a journal of neurology2021
Annexin A1 restores cerebrovascular integrity concomitant with reduced amyloid-β and tau pathology.
Article in Brain : a journal of neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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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
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Proteins and Transcriptional Dysregulation of the Brain Extracellular Matrix in Parkinson's Disease: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- The role of Annexin A2 in Alzheimer's disease: From cellular functions to therapeutic potential.The FEBS journal · 2026Review
- Annexin A1 in Alzheimer's disease: A new therapeutic strategy focusing on neuroinflammation.Neural regeneration research · 2026Article
- Exploring the Expression Changes of Immune Genes in Alzheimer's Disease: A Study on ANXA1, VCAM1, and CCL2.Molecular neurobiology · 2026Article
- From brain to eye: Annexin A1 and A2 as a key mediator of retinal neuroinflammation in Parkinson's and Alzheimer's disease.International journal of retina and vitreous · 2026Article
- Single-cell RNA sequencing reveals disease associated changes in brain endothelial cells in the 5XFAD mouse.Fluids and barriers of the CNS · 2026Article
- Biomimetic core-shell GelMA microspheres co-delivering ANXA1, NGF, and fibronectin enable phase-matched immunomodulation and neurorepair after spinal cord injury.Theranostics · 2026Article
- Chemical Exchange Saturation Transfer Imaging in Neuroinflammation: Methods, Challenges, and Recommendations.International journal of molecular sciences · 2025Review
- Cyclooxygenase-1 deletion in 5 × FAD mice protects against microglia-induced neuroinflammation and mitigates cognitive impairment.Translational neurodegeneration · 2025Article
- Trimethylamine N-Oxide Mitigates Perioperative Neurocognitive Disorders via ANXA1 Nuclear Translocation and M2 Microglial Polarization in the Hippocampus.CNS neuroscience & therapeutics · 2025Article
- Annexin A6 membrane repair protein protects against amyloid-induced dystrophic neurites and tau phosphorylation in Alzheimer's disease model mice.Acta neuropathologica · 2025Article
- Integrative single-cell RNA sequencing and mendelian randomization analysis reveal the potential role of synaptic vesicle cycling-related genes in Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2025Article
- The Protective Effect of Annexin A1 on Autophagy Via the CAMK2/BECN1 Signaling Pathway in PC12 Cells Stimulated with HNeurotoxicity research · 2025Article
- Blood-brain barrier disruption: a pervasive driver and mechanistic link between traumatic brain injury and Alzheimer's disease.Translational neurodegeneration · 2025Review
- The interaction between dysfunction of vasculature and tauopathy in Alzheimer's disease and related dementias.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Prenatal Stress Increases the Risk of the FPR2-related Dysfunction in the Brain's Resolution of Inflammation: A Study on the Humanized APPCurrent neuropharmacology · 2025Article
- Saliva Proteome, Metabolome and Microbiome Signatures for Detection of Alzheimer's Disease.Metabolites · 2024Article
- Plasma membrane repair defect in Alzheimer's disease neurons is driven by the reduced dysferlin expression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Single-Cell RNA Sequencing Reveals Immunomodulatory Effects of Stem Cell Factor and Granulocyte Colony-Stimulating Factor Treatment in the Brains of Aged APP/PS1 Mice.Biomolecules · 2024Article
- Maf1 loss regulates spinogenesis and attenuates cognitive impairment in Alzheimer's disease.Brain : a journal of neurology · 2024Article
Corrections and comments
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Authors and funding
22 authors at 5 institutions in 4 countries.
Funding
Abstract
Alzheimer's disease, characterized by brain deposits of amyloid-β plaques and neurofibrillary tangles, is also linked to neurovascular dysfunction and blood-brain barrier breakdown, affecting the passage of substances into and out of the brain. We hypothesized that treatment of neurovascular alterations could be beneficial in Alzheimer's disease. Annexin A1 (ANXA1) is a mediator of glucocorticoid anti-inflammatory action that can suppress microglial activation and reduce blood-brain barrier leakage. We have reported recently that treatment with recombinant human ANXA1 (hrANXA1) reduced amyloid-β levels by increased degradation in neuroblastoma cells and phagocytosis by microglia. Here, we show the beneficial effects of hrANXA1 in vivo by restoring efficient blood-brain barrier function and decreasing amyloid-β and tau pathology in 5xFAD mice and Tau-P301L mice. We demonstrate that young 5xFAD mice already suffer cerebrovascular damage, while acute pre-administration of hrANXA1 rescued the vascular defects. Interestingly, the ameliorated blood-brain barrier permeability in young 5xFAD mice by hrANXA1 correlated with reduced brain amyloid-β load, due to increased clearance and degradation of amyloid-β by insulin degrading enzyme (IDE). The systemic anti-inflammatory properties of hrANXA1 were also observed in 5xFAD mice, increasing IL-10 and reducing TNF-α expression. Additionally, the prolonged treatment with hrANXA1 reduced the memory deficits and increased synaptic density in young 5xFAD mice. Similarly, in Tau-P301L mice, acute hrANXA1 administration restored vascular architecture integrity, affecting the distribution of tight junctions, and reduced tau phosphorylation. The combined data support the hypothesis that blood-brain barrier breakdown early in Alzheimer's disease can be restored by hrANXA1 as a potential therapeutic approach.
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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.