ArticleScientific reports2022
Increased Type I interferon signaling and brain endothelial barrier dysfunction in an experimental model of Alzheimer's disease.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 42 citations in OpenAlex.
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- Restores Aβ Clearance by Overcoming PCSK9-LRP1 Dysregulation and TRIB3-Mediated Autophagy Blockade in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Distinct and combined interferon-ɑ/β-receptor-1 loss in neurons and astrocytes disrupt brain energy metabolism and drive Parkinsonian dementia.Journal of biomedical science · 2026Article
- Type-1 interferons associated with microglial-mediated neuroinflammation in Alzheimer's disease.Journal of neuroinflammation · 2026Review
- Endothelial IRE1 signaling maintains blood-brain barrier integrity and limits neuroinflammation after traumatic brain injury.Cell death & disease · 2026Article
- Deficiency of Smooth Muscle Adar1 Exacerbates Vascular Remodeling and Pulmonary Hypertension.Circulation research · 2026Article
- Blood-brain barrier dysfunction and peripheral immune activation in Alzheimer's disease: an inflammation-centered review.Frontiers in immunology · 2026Review
- Microbiota-specific serum IgG links gut and joints through immune-endothelial crosstalk in arthritis.Frontiers in microbiology · 2026Article
- The Alzheimer's therapeutic Lecanemab attenuates Aβ pathology by inducing an amyloid-clearing program in microglia.Nature neuroscience · 2026Article
- Neuroimmune mechanisms of neuropsychiatric systemic lupus erythematosus.Current opinion in immunology · 2025Review
- Emerging roles for innate and adaptive immunity in tauopathies.Cell reports · 2025Review
- Endothelial delivery of simvastatin by LRP1-targeted nanoparticles ameliorates pathogenesis of alzheimer's disease in a mouse model.Alzheimer's research & therapy · 2025Article
- Restoring brain barriers: an innovative approach for treating neurological disorders.Fluids and barriers of the CNS · 2025Review
- SARS-CoV-2 infection of human cortical cells is influenced by the interaction between aneuploidy and biological sex: insights from a Down syndrome in vitro model.Acta neuropathologica · 2025Article
- The Ever-Expanding Influence of the Endothelial Nitric Oxide Synthase.Basic & clinical pharmacology & toxicology · 2025Review
- Pericytes: The forgotten controllers of a functional blood-brain barrier.PLoS pathogens · 2025Article
- Cell-specific transcriptional signatures of vascular cells in Alzheimer's disease: perspectives, pathways, and therapeutic directions.Molecular neurodegeneration · 2025Review
- Microglial NLRP3-gasdermin D activation impairs blood-brain barrier integrity through interleukin-1β-independent neutrophil chemotaxis upon peripheral inflammation in mice.Nature communications · 2025Article
- Microglia drive diurnal variation in susceptibility to inflammatory blood-brain barrier breakdown.JCI insight · 2024Article
- Noncanonical functions of adhesion proteins in inflammation.American journal of physiology. Cell physiology · 2024Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Blood-brain barrier (BBB) dysfunction is emerging as a key pathogenic factor in the progression of Alzheimer's disease (AD), where increased microvascular endothelial permeability has been proposed to play an important role. However, the molecular mechanisms leading to increased brain microvascular permeability in AD are not fully understood. We studied brain endothelial permeability in female APPswe/PS1∆E9 (APP/PS1) mice which constitute a transgenic mouse model of amyloid-beta (Aβ) amyloidosis and found that permeability increases with aging in the areas showing the greatest amyloid plaque deposition. We performed an unbiased bulk RNA-sequencing analysis of brain endothelial cells (BECs) in female APP/PS1 transgenic mice. We observed that upregulation of interferon signaling gene expression pathways in BECs was among the most prominent transcriptomic signatures in the brain endothelium. Immunofluorescence analysis of isolated BECs from female APP/PS1 mice demonstrated higher levels of the Type I interferon-stimulated gene IFIT2. Immunoblotting of APP/PS1 BECs showed downregulation of the adherens junction protein VE-cadherin. Stimulation of human brain endothelial cells with interferon-β decreased the levels of the adherens junction protein VE-cadherin as well as tight junction proteins Occludin and Claudin-5 and increased barrier leakiness. Depletion of the Type I interferon receptor in human brain endothelial cells prevented interferon-β-induced VE-cadherin downregulation and restored endothelial barrier integrity. Our study suggests that Type I interferon signaling contributes to brain endothelial dysfunction in AD.
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