ArticleThe American journal of pathology2010
Brain endothelial cells synthesize neurotoxic thrombin in Alzheimer's disease.
Article in The American journal of pathology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01361763 (Phase II, Randomized, Crossover, Single Blind, Safety Trial of DABIGATRAN Versus ASA for Preventing Ischaemic Brain Lesions in Patients Affected by CADASIL), which is not on this map. Cited by 51 papers.
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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.
Phase II, Randomized, Crossover, Single Blind, Safety Trial of DABIGATRAN Versus ASA for Preventing Ischaemic Brain Lesions in Patients Affected by CADASIL
Who cites it
51 citing papers in PubMed, 102 citations in OpenAlex.
- Alzheimer's Disease-Thrombosis Comorbidity: A Growing Body of Evidence from Patients and Animal Models.Cells · 2025Review
- Activation of the Coagulation Cascade as a Universal Danger Sign.Current issues in molecular biology · 2025Review
- Improvements in Exercise for Alzheimer's Disease: Highlighting FGF21-Induced Cerebrovascular Protection.Neurochemical research · 2025Review
- Endothelial Dysfunctions in Blood-Brain Barrier Breakdown in Alzheimer's Disease: From Mechanisms to Potential Therapies.CNS neuroscience & therapeutics · 2024Review
- Cellular and molecular mechanisms of the blood-brain barrier dysfunction in neurodegenerative diseases.Fluids and barriers of the CNS · 2024Review
- Thinking outside the black box: are the brain endothelial cells the new main target in Alzheimer's disease?Neural regeneration research · 2023Review
- Post-transcriptional control of haemostatic genes: mechanisms and emerging therapeutic concepts in thrombo-inflammatory disorders.Cardiovascular research · 2023Review
- Review
- Involvement of an Aberrant Vascular System in Neurodevelopmental, Neuropsychiatric, and Neuro-Degenerative Diseases.Life (Basel, Switzerland) · 2023Review
- Effects of Thrombin on the Neurovascular Unit in Cerebral Ischemia.Cellular and molecular neurobiology · 2022Review
- A Leaky Blood-Brain Barrier to Fibrinogen Contributes to Oxidative Damage in Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2021Review
- Cerebrovascular phenotypes in mouse models of Alzheimer's disease.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Review
- Impact of Cardiovascular Hemodynamics on Cognitive Aging.Arteriosclerosis, thrombosis, and vascular biology · 2021Review
- Human Tau Isoforms and Proteolysis for Production of Toxic Tau Fragments in Neurodegeneration.Frontiers in neuroscience · 2021Review
- Role of the Extracellular Traps in Central Nervous System.Frontiers in immunology · 2021Review
- Why TDP-43? Why Not? Mechanisms of Metabolic Dysfunction in Amyotrophic Lateral Sclerosis.Neuroscience insights · 2020Review
- Caveolae, CD109, and endothelial cells as targets for treating Alzheimer's disease.Alzheimer's & dementia (New York, N. Y.) · 2020Article
- Thrombin, a Mediator of Coagulation, Inflammation, and Neurotoxicity at the Neurovascular Interface: Implications for Alzheimer's Disease.Frontiers in neuroscience · 2020Review
- Molecular chaperones in the brain endothelial barrier: neurotoxicity or neuroprotection?FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Review
- Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Alzheimer's disease (AD) is characterized by neuronal death; thus, identifying neurotoxic proteins and their source is central to understanding and treating AD. The multifunctional protease thrombin is neurotoxic and found in AD senile plaques. The objective of this study was to determine whether brain endothelial cells can synthesize thrombin and thus be a source of this neurotoxin in AD brains. Microvessels were isolated from AD patient brains and from age-matched controls. Reverse transcription-PCR demonstrated that thrombin message was highly expressed in microvessels from AD brains but was not detectable in control vessels. Similarly, Western blot analysis of microvessels showed that the thrombin protein was highly expressed in AD- but not control-derived microvessels. In addition, high levels of thrombin were detected in cerebrospinal fluid obtained from AD but not control patients, and sections from AD brains showed reactivity to thrombin antibody in blood vessel walls but not in vessels from controls. Finally, we examined the ability of brain endothelial cells in culture to synthesize thrombin and showed that oxidative stress or cell signaling perturbations led to increased expression of thrombin mRNA in these cells. The results demonstrate, for the first time, that brain endothelial cells can synthesize thrombin, and suggest that novel therapeutics targeting vascular stabilization that prevent or decrease release of thrombin could prove useful in treating this neurodegenerative disease.
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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.