ArticleProceedings of the National Academy of Sciences of the United States of America2020
Cerebral amyloid angiopathy-linked β-amyloid mutations promote cerebral fibrin deposits via increased binding affinity for fibrinogen.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 43 citations in OpenAlex.
- Molecular Pathogenesis of Cerebral Amyloid Angiopathy in Alzheimer's Disease: The Role of the Central Fibrinolytic Cascade at the Neurovascular Unit.Molecular neurobiology · 2026Review
- SARS-CoV-2 spike protein does not alter plasma fibrin clots.Blood advances · 2026Article
- Unveiling the procoagulant state in Alzheimer's disease: A novel PET imaging strategy.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Therapeutic targeting of fibrin-microglia interactions ameliorates Alzheimer's disease-related hyperexcitability and brain network dysfunction.bioRxiv : the preprint server for biology · 2026Article
- SARS-CoV-2 Spike Protein Amyloid Fibrils Impair Fibrin Formation and Fibrinolysis.Biochemistry · 2025Article
- Pathological mechanisms of motor dysfunction in familial Danish dementia: insights from a knock-in rat model.Journal of neuroinflammation · 2025Article
- Higher phosphorylated tau levels predict cognitive decline and amyloid-related imaging abnormalities during lecanemab treatment: clinical practice data.Alzheimer's research & therapy · 2025Article
- Alzheimer's Disease-Thrombosis Comorbidity: A Growing Body of Evidence from Patients and Animal Models.Cells · 2025Review
- Synergistic effects of the Aβ/fibrinogen complex on synaptotoxicity, neuroinflammation, and blood-brain barrier damage in Alzheimer's disease models.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Proteomic Evidence for Amyloidogenic Cross-Seeding in Fibrinaloid Microclots.International journal of molecular sciences · 2024Article
- Elevated protease-activated receptor 4 (PAR4) gene expression in Alzheimer's disease predicts cognitive decline.Neurobiology of aging · 2024Article
- Is CAA a perivascular brain clearance disease? A discussion of the evidence to date and outlook for future studies.Cellular and molecular life sciences : CMLS · 2024Review
- Clinical considerations in early-onset cerebral amyloid angiopathy.Brain : a journal of neurology · 2023Review
- Primary Hypothyroidism and Alzheimer's Disease: A Tale of Two.Cellular and molecular neurobiology · 2023Review
- Tranexamic acid in a mouse model of cerebral amyloid angiopathy: setting the stage for a novel stroke treatment approach.Research and practice in thrombosis and haemostasis · 2023Article
- Vascular Dysfunction in Alzheimer's Disease: Alterations in the Plasma Contact and Fibrinolytic Systems.International journal of molecular sciences · 2023Review
- Fibrin-Targeting Immunotherapy for Dementia.The journal of prevention of Alzheimer's disease · 2023Article
- Striatal fibrinogen extravasation and vascular degeneration correlate with motor dysfunction in an aging mouse model of Alzheimer's disease.Frontiers in aging neuroscience · 2023Article
- Regional contribution of vascular dysfunction in white matter dementia: clinical and neuropathological insights.Frontiers in neurology · 2023Review
- Dissecting Polygenic Etiology of Ischemic Stroke in the Era of Precision Medicine.Journal of clinical medicine · 2022Review
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5 authors at 3 institutions in 2 countries.
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Abstract
Cerebral amyloid angiopathy (CAA), where beta-amyloid (Aβ) deposits around cerebral blood vessels, is a major contributor of vascular dysfunction in Alzheimer's disease (AD) patients. However, the molecular mechanism underlying CAA formation and CAA-induced cerebrovascular pathology is unclear. Hereditary cerebral amyloid angiopathy (HCAA) is a rare familial form of CAA in which mutations within the (Aβ) peptide cause an increase in vascular deposits. Since the interaction between Aβ and fibrinogen increases CAA and plays an important role in cerebrovascular damage in AD, we investigated the role of the Aβ-fibrinogen interaction in HCAA pathology. Our work revealed the most common forms of HCAA-linked mutations, Dutch (E22Q) and Iowa (D23N), resulted in up to a 50-fold stronger binding affinity of Aβ for fibrinogen. In addition, the stronger interaction between fibrinogen and mutant Aβs led to a dramatic perturbation of clot structure and delayed fibrinolysis. Immunofluorescence analysis of the occipital cortex showed an increase of fibrin(ogen)/Aβ codeposition, as well as fibrin deposits in HCAA patients, compared to early-onset AD patients and nondemented individuals. Our results suggest the HCAA-type Dutch and Iowa mutations increase the interaction between fibrinogen and Aβ, which might be central to cerebrovascular pathologies observed in HCAA.
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