ArticleProceedings of the National Academy of Sciences of the United States of America2018
Blood-derived plasminogen drives brain inflammation and plaque deposition in a mouse model of Alzheimer's disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
What it found
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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
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Alpha2-Antiplasmin: The Devil You Don't Know in Cerebrovascular and Cardiovascular Disease.Frontiers in cardiovascular medicine · 2020Pooled it
- The Double-Edged Sword Effect of the Fibrinolytic System in Alzheimer's Disease.Cellular and molecular neurobiology · 2026Review
- Rather a versatile multi-tool than a sword: an integral role of the plasminogen system in health and disease.Frontiers in immunology · 2026Review
- Tranexamic acid does not have a dose-dependent effect on postoperative delirium after cardiac surgery - a retrospective cohort study.The journal of extra-corporeal technology · 2025Observational
- Article
- Biomimetic engineering of a neuroinflammation-targeted MOF nanozyme scaffolded with photo-trigger released CO for the treatment of Alzheimer's disease.Chemical science · 2024Article
- RNA therapeutics to control fibrinolysis: review on applications in biology and medicine.Journal of thrombosis and haemostasis : JTH · 2024Review
- Proteomics of human platelet lysates and insight from animal studies on platelet protein diffusion to hippocampus upon intranasal administration.APL bioengineering · 2024Article
- Plasminogen deficiency suppresses pancreatic ductal adenocarcinoma disease progression.Molecular oncology · 2024Article
- Cerebrospinal Fluid Proteomic Profiles in Patients with Postherpetic Neuralgia.Journal of proteome research · 2023Article
- Mechanisms underlying HIV-associated cognitive impairment and emerging therapies for its management.Nature reviews. Neurology · 2023Review
- Identification of Plasma Proteins as Biomarkers for Mild Cognitive Impairment and Alzheimer's Disease Using Liquid Chromatography-Tandem Mass Spectrometry.International journal of molecular sciences · 2023Article
- Pathophysiological Role of Microglial Activation Induced by Blood-Borne Proteins in Alzheimer's Disease.Biomedicines · 2023Review
- Vascular Dysfunction in Alzheimer's Disease: Alterations in the Plasma Contact and Fibrinolytic Systems.International journal of molecular sciences · 2023Review
- pKr-2 induces neurodegenerationBrain, behavior, & immunity - health · 2023Article
- Immune-metabolic mechanisms of post-traumatic stress disorder and atherosclerosis.Frontiers in physiology · 2023Review
- Pathological changes within the cerebral vasculature in Alzheimer's disease: New perspectives.Brain pathology (Zurich, Switzerland) · 2022Review
- Serpin Signatures in Prion and Alzheimer's Diseases.Molecular neurobiology · 2022Article
- Exerkines in health, resilience and disease.Nature reviews. Endocrinology · 2022Review
- Nrf2 activator PB125® as a carnosic acid-based therapeutic agent against respiratory viral diseases, including COVID-19.Free radical biology & medicine · 2021Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Two of the most predominant features of the Alzheimer's disease (AD) brain are deposition of β-amyloid (Aβ) plaques and inflammation. The mechanism behind these pathologies remains unknown, but there is evidence to suggest that inflammation may predate the deposition of Aβ. Furthermore, immune activation is increasingly being recognized as a major contributor to the pathogenesis of the disease, and disorders involving systemic inflammation, such as infection, aging, obesity, atherosclerosis, diabetes, and depression are risk factors for the development of AD. Plasminogen (PLG) is primarily a blood protein synthesized in the liver, which when cleaved into its active form, plasmin (PL), plays roles in fibrinolysis, wound healing, cell signaling, and inflammatory regulation. Here we show that PL in the blood is a regulator of brain inflammatory action and AD pathology. Depletion of PLG in the plasma of an AD mouse model through antisense oligonucleotide technology dramatically improved AD pathology and decreased glial cell activation in the brain, whereas an increase in PL activity through α-2-antiplasmin (A2AP) antisense oligonucleotide treatment exacerbated the brain's immune response and plaque deposition. These studies suggest a crucial role for peripheral PL in mediating neuroimmune cell activation and AD progression and could provide a link to systemic inflammatory risk factors that are known to be associated with AD development.
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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.