Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Brain perfusion and blood-brain barrier (BBB) integrity are reduced early in Alzheimer's disease (AD). We performed single nucleus RNA sequencing of vascular cells isolated from AD and non-diseased control brains to characterise pathological transcriptional signatures responsible for this. We show that endothelial cells (EC) are enriched for expression of genes associated with susceptibility to AD. Increased β-amyloid is associated with BBB impairment and a dysfunctional angiogenic response related to a failure of increased pro-angiogenic HIF1A to increased VEGFA signalling to EC. This is associated with vascular inflammatory activation, EC senescence and apoptosis. Our genomic dissection of vascular cell risk gene enrichment provides evidence for a role of EC pathology in AD and suggests that reducing vascular inflammatory activation and restoring effective angiogenesis could reduce vascular dysfunction contributing to the genesis or progression of early AD.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10933340 | PMC |
| http://dx.doi.org/10.1038/s41467-024-46630-z | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Intestinal epithelial Dicer1 regulates gut microbiome and Alzheimer's pathology in App-knock-in mice.
Alzheimers Res Ther
September 2025
Department of Neurology, Saarland University, Kirrberger Straße, 66421, Homburg/Saar, Germany.
Background: Alzheimer's disease (AD) patients and animal models exhibit an altered gut microbiome that is associated with pathological changes in the brain. Intestinal miRNA enters bacteria and regulates bacterial metabolism and proliferation. This study aimed to investigate whether the manipulation of miRNA could alter the gut microbiome and AD pathologies.
View Article and Find Full Text PDFGestational hypoxia increases brain-blood barrier permeability in the neonatal cerebral cortex of Guinea pigs.
Pediatr Res
September 2025
Laboratory of Fetal Neuroprogramming, Institute of Health Sciences, University of O'Higgins, Rancagua, Chile.
Background: Fetal growth restriction (FGR) causes an adaptive redistribution of the cardiac output towards sustained cerebral vasodilation. However, the consequences of FGR and cerebral vasodilatation due to fetal hypoxia on the blood-brain barrier (BBB) are still poorly studied. This study assesses BBB permeability in the neonatal cortex of pups gestated under intrauterine hypobaric hypoxia.
View Article and Find Full Text PDFKCC-07, MBD2 Inhibitor, Expands the Therapeutic Window of DNA Damage Inducing Reagents in Neural Tumor Cells.
Exp Neurobiol
August 2025
Institute of Medical Science, Ajou University School of Medicine, Suwon 16499, Korea.
Neural tumors represent diverse malignancies with distinct molecular profiles and present particular challenges due to the blood-brain barrier, heterogeneous molecular etiology including epigenetic dysregulation, and the affected organ's critical nature. KCC-07, a selective and blood-brain barrier penetrable MBD2 (methyl CpG binding domain protein 2) inhibitor, can suppress tumor development by inducing p53 signaling, proven only in medulloblastoma. Here we demonstrate KCC-07 treatment's application to other neural tumors.
View Article and Find Full Text PDFAge-related changes in cardiolipin profile and functional consequences of altered fatty acid supply.
Biochim Biophys Acta Mol Cell Biol Lipids
September 2025
Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Am Klinikum 1, 07747, Jena, Germany; Center for Molecular Biomedicine, Jena University Hospital, Hans-Knöll-Str. 2, 07745, Jena, Germany; Center for Sepsis Control and Care, Jena University Hospital, Am Klinikum 1,
Cardiolipins (CLs) are primarily expressed in the inner mitochondrial membrane where they play essential roles in membrane architecture and mitochondrial functions. CLs have a unique structure characterized by four acyl chains with different stoichiometries such as chain length and degree of saturation. CL composition changes with disease and age, but it is largely unknown how dynamic changes affect mitochondrial function.
View Article and Find Full Text PDFHeat stroke-induced central nervous system injury: Mechanisms and therapeutic perspectives.
J Therm Biol
September 2025
Department of Critical Care Medicine, the First Medical Cener, Chinese PLA General Hospital, Beijing, 100853, China. Electronic address:
Heat stroke (HS), a life-threatening heat-related disorder, is characterized by a rapid elevation of core body temperature exceeding 40 °C, accompanied by central nervous system (CNS) dysfunction and multiple organ dysfunction syndrome (MODS). With the escalating impact of global warming, the incidence of HS has risen progressively, posing a significant threat to global health. The CNS is one of the primary target organs in HS, and its injury mechanisms involve intricate interactions among inflammatory cascades, oxidative stress, programmed cell death, and blood-brain barrier (BBB) disruption.
View Article and Find Full Text PDF