ArticleScientific reports2021
Elevated complement mediator levels in endothelial-derived plasma exosomes implicate endothelial innate inflammation in diminished brain function of aging humans.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
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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.
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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
17 citing papers in PubMed, 21 citations in OpenAlex.
- The vascular contribution to dementia: World Stroke Organization scientific statement.International journal of stroke : official journal of the International Stroke Society · 2026Review
- Extracellular Vesicles in Stroke: Drivers of Brain-Body Network Crosstalk.Translational stroke research · 2026Review
- Quantifying White Matter Hyperintensities: Automated Volumetry Compared with Visual Grading Scales.Medicina (Kaunas, Lithuania) · 2025Article
- Inflammation and Cognitive Decline: A Population-Based Cohort Study Among Aging Adults With Atrial Fibrillation.Journal of the American Heart Association · 2025Article
- WMH Contributions to Cognitive Impairment: Rationale and Design of the Diverse VCID Study.Stroke · 2025Review
- Exosomal-complement system activation in preeclampsia.The journal of obstetrics and gynaecology research · 2025Review
- Alterations of the blood-brain barrier during aging.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Review
- White Matter Hyperintensities: Complex Predictor of Complex Outcomes.Journal of the American Heart Association · 2023Article
- Clinical trials in vascular cognitive impairment following SPRINT-MIND: An international perspective.Cell reports. Medicine · 2023Review
- Global Research Trends of Exosomes in the Central Nervous System: A Bibliometric and Visualized Analysis.Neurospine · 2023Article
- Complement protein levels in serum astrocyte-derived exosomes are associated with cognitive impairment in obstructive sleep apnea.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2023Article
- Plasma derived extracellular vesicle biomarkers of microglia activation in an experimental stroke model.Journal of neuroinflammation · 2023Article
- COVID, complement, and the brain.Frontiers in immunology · 2023Review
- Review
- Review
- Emerging Antioxidant Paradigm of Mesenchymal Stem Cell-Derived Exosome Therapy.Frontiers in endocrinology · 2021Review
- Hippocampal mediation in the lipid-Alzheimer's disease pathway: A high-dimensional mediation analysis stratified byAlzheimer's & dementia (New York, N. Y.)Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
We test the hypothesis that endothelial cells adopt an inflammatory phenotype in functionally intact aged human subjects with radiographic evidence of white matter hyperintensity (WMH) suggestive of small cerebrovascular disease. Components of all three complement effector pathways and regulatory proteins were quantified in extracts of plasma endothelial-derived exosomes (EDE) of 11 subjects (age 70-82) with and 15 without evidence of WMH on MRI. Group differences and associations with plasma markers of immune activation (IL6, ICAM1), cognition and neuroimaging were calculated via regression modelling. EDE complement factors within the alternative and classical pathways were found to be higher and regulatory proteins lower in subjects with WMH. EDE levels of some complement components demonstrated significant associations with cognitive slowing and elevated systolic blood pressure. The inhibitor of the membrane attack complex, CD46, showed a significant positive association with cerebral grey matter volume. Plasma inflammatory markers, IL6 and ICAM1, were positively associated with EDE levels of several complement components. These findings provide the first in vivo evidence of the association of endothelial cell inflammation with white matter disease, age-associated cognitive changes, and brain degeneration in functionally normal older individuals. Future endothelial biomarker development may permit recognition of early or preclinical stages of vascular contributions to cognitive impairment and dementia.
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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.