ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025
Synergistic effects of the Aβ/fibrinogen complex on synaptotoxicity, neuroinflammation, and blood-brain barrier damage in Alzheimer's disease models.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- SARS-CoV-2 spike protein does not alter plasma fibrin clots.Blood advances · 2026Article
- CSF fibrinogen predicts longitudinal Tau accumulation in cognitively unimpaired older adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 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
- Cholesterol metabolism in neurodegenerative diseases: mechanisms and therapeutic advances.Molecular neurodegeneration · 2026Review
- Review
- Review
- The Double-Edged Sword Effect of the Fibrinolytic System in Alzheimer's Disease.Cellular and molecular neurobiology · 2026Review
- Molecular design of MRI probes for targeting amyloid-β species: fromTheranostics · 2026Review
- Blood-brain barrier dysfunction and peripheral immune activation in Alzheimer's disease: an inflammation-centered review.Frontiers in immunology · 2026Review
- Alzheimer's Disease: From Molecular Pathogenesis to Disease-Modifying Therapies and Clinical Implementation in Aging Populations.Clinical interventions in aging · 2026Review
- Natural Chiral Scaffolds in Alzheimer's Disease: Therapeutic Potential, Mechanism, and Clinical Aspects.BioMed research international · 2026Review
- SARS-CoV-2 Spike Protein Amyloid Fibrils Impair Fibrin Formation and Fibrinolysis.Biochemistry · 2025Article
- A proteomic signature of vascular dysfunction linked to tauopathy and degeneration in the aging brain.bioRxiv : the preprint server for biology · 2025Article
- 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
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Authors and funding
5 authors.
Funding
Abstract
introductionAlzheimer's disease (AD) is characterized by amyloid-beta (Aβ), hyperphosphorylated tau, chronic neuroinflammation, blood-brain barrier (BBB) damage, and synaptic dysfunction, leading to neuronal loss and cognitive deficits. Vascular proteins, including fibrinogen, extravasate into the brain, further contributing to damage and inflammation. Fibrinogen's interaction with Aβ is well-established, but how this interaction contributes to synaptic dysfunction in AD is unknown.
methodsOrganotypic hippocampal cultures (OHC) were exposed to Aβ42 oligomers, fibrinogen, or Aβ42/fibrinogen complexes. Synaptotoxicity was analyzed by Western blot. Aβ42 oligomers, fibrinogen, or their complexes were intracerebroventricularly injected into mice. Histopathological AD markers, synaptotoxicity, neuroinflammation, and vascular markers were observed by Western blot and immunofluorescence.
resultsAβ42/fibrinogen complexes led to synaptic loss, tau181 phosphorylation, neuroinflammation, and BBB disruption, independent of Mac1/CD11b receptor signaling. Blocking Aβ42/fibrinogen complex formation prevented synaptotoxicity. DISCUSSION: These findings indicate that the Aβ42/fibrinogen complex has a synergistic impact on hippocampal synaptotoxicity and neuroinflammation. HIGHLIGHTS: Fibrinogen binds to the central region of Aβ, forming a plasmin-resistant complex. The Aβ/fibrinogen complex induces synaptotoxicity, inflammation, and BBB disruption. Synaptotoxicity induced by the complex is independent of Mac1 receptor signaling.
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