ArticleProceedings of the National Academy of Sciences of the United States of America2015
Activation of the factor XII-driven contact system in Alzheimer's disease patient and mouse model plasma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 110 citations in OpenAlex.
- Development of an Interpretable QSAR Model for Predicting Coagulation Factor XIIa Inhibitors Using Ensemble Machine Learning.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Bradykinin contributes to vasogenic edema in murine experimental cerebral malaria.The Journal of clinical investigation · 2026Article
- Article
- Molecular pathogenesis of Alzheimer's disease onset in a mouse model: effects of cannabidiol treatment.Frontiers in neuroscience · 2025Article
- Review
- Endothelial Dysfunctions in Blood-Brain Barrier Breakdown in Alzheimer's Disease: From Mechanisms to Potential Therapies.CNS neuroscience & therapeutics · 2024Review
- Bat-derived oligopeptide LE6 inhibits the contact-kinin pathway and harbors anti-thromboinflammation and stroke potential.Zoological research · 2024Article
- Bradykinin promotes immune responses in differentiated embryonic neurospheres carrying APPCell & bioscience · 2024Article
- Innate neuroimmunity across aging and neurodegeneration: a perspective from amyloidogenic evolvability.Frontiers in cell and developmental biology · 2024Review
- A possible mechanism for the enhanced toxicity of beta-amyloid protofibrils in Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Dementia in Diabetes: The Role of Hypoglycemia.International journal of molecular sciences · 2023Review
- Review
- Vascular Dysfunction in Alzheimer's Disease: Alterations in the Plasma Contact and Fibrinolytic Systems.International journal of molecular sciences · 2023Review
- Triazol-1-yl Benzamides Promote Anticoagulant ActivityCardiovascular & hematological agents in medicinal chemistry · 2023Article
- A new perspective on Alzheimer's disease: microRNAs and circular RNAs.Frontiers in genetics · 2023Review
- 6-(Arylaminomethyl) Isoquinolines as Enzyme Inhibitors and Their Preparation: A Patent Highlight of Factor XIIa Inhibitors.Cardiovascular & hematological agents in medicinal chemistry · 2023Article
- Dysregulated haemostasis in thrombo-inflammatory disease.Clinical science (London, England : 1979) · 2022Review
- Blocking domain 6 of high molecular weight kininogen to understand intrinsic clotting mechanisms.Research and practice in thrombosis and haemostasis · 2022Article
- Direct Oral Anticoagulants (DOACs) for Therapeutic Targeting of Thrombin, a Key Mediator of Cerebrovascular and Neuronal Dysfunction in Alzheimer's Disease.Biomedicines · 2022Review
- Anti-HK antibody reveals critical roles of a 20-residue HK region for Aβ-induced plasma contact system activation.Blood advances · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 3 countries.
Funding
Abstract
Alzheimer's disease (AD) is characterized by accumulation of the β-amyloid peptide (Aβ), which likely contributes to disease via multiple mechanisms. Increasing evidence implicates inflammation in AD, the origins of which are not completely understood. We investigated whether circulating Aβ could initiate inflammation in AD via the plasma contact activation system. This proteolytic cascade is triggered by the activation of the plasma protein factor XII (FXII) and leads to kallikrein-mediated cleavage of high molecular-weight kininogen (HK) and release of proinflammatory bradykinin. Aβ has been shown to promote FXII-dependent cleavage of HK in vitro. In addition, increased cleavage of HK has been found in the cerebrospinal fluid of patients with AD. Here, we show increased activation of FXII, kallikrein activity, and HK cleavage in AD patient plasma. Increased contact system activation is also observed in AD mouse model plasma and in plasma from wild-type mice i.v. injected with Aβ42. Our results demonstrate that Aβ42-mediated contact system activation can occur in the AD circulation and suggest new pathogenic mechanisms, diagnostic tests, and therapies for AD.
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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.