ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2013
The APOE ɛ4/ɛ4 genotype potentiates vascular fibrin(ogen) deposition in amyloid-laden vessels in the brains of Alzheimer's disease patients.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 1 of them a synthesis that pooled it.
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Who cites it
114 citing papers in PubMed, 1 synthesis or guideline pooled it, 179 citations in OpenAlex.
- Markers of microglia in post-mortem brain samples from patients with Alzheimer's disease: a systematic review.Molecular psychiatry · 2018Pooled it
- Tiered Evaluation of Carbosilane Dendrimer-siRNA Nanoplatform from Single-Cell Biocompatibility to Blood-Brain Barrier Model Dynamics and Murine Alzheimer Model Behavior Assessment.ACS applied materials & interfaces · 2026Article
- Elevated levels of circulating plasma sPDGFRβ in cognitively impaired APOE4 carriers.GeroScience · 2026Article
- Increased neurotoxic gliosis and blood-brain barrier dysregulation in canine cognitive dysfunction syndrome (CCD).Frontiers in aging · 2026Article
- Crossroads of well-being: oral health, neurology, neuronutrition and healthy aging.Open medicine (Warsaw, Poland) · 2026Review
- Exploring cellular heterogeneity: single-cell and spatial transcriptomics of Alzheimer's disease brains and iPSC-derived microglia.Alzheimer's research & therapy · 2025Article
- AmyloGram reveals amyloidogenic potential in stroke thrombus proteomes.The Biochemical journal · 2025Article
- APOE-Targeted Therapeutics for Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- Integrated machine learning identifies biomarkers for bilirubin-induced Alzheimer's disease-like lesions in neonates and adults.Scientific reports · 2025Article
- Memory deficits in hypertensive ApoE4 mice reversed by P2Y12 inhibition via different mechanisms in males and perimenopausal females.Research square · 2025Article
- Navigation Between Alzheimer's Disease (AD) and Its Various Pathophysiological Trajectories: The Pathogenic Link to Neuroimmunology-Genetics and Neuroinflammation.International journal of molecular sciences · 2025Review
- Bone marrow-derived myeloid cells drive neuroinflammation in Alzheimer's disease: Insights from the FADJournal of orthopaedic translation · 2025Article
- Inhibiting 15-PGDH blocks blood-brain barrier deterioration and protects mice from Alzheimer's disease and traumatic brain injury.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The microcirculation, the blood-brain barrier, and the neurovascular unit in health and Alzheimer disease: The aberrant pericyte is a central player.Pharmacological reviews · 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
- Molecular and cellular characteristics of cerebrovascular cell types and their contribution to neurodegenerative diseases.Molecular neurodegeneration · 2025Review
- Oral microbiome and nitric oxide biomarkers in older people with mild cognitive impairment andPNAS nexus · 2025Article
- Machine learning reveals prominent spontaneous behavioral changes and treatment efficacy in humanized and transgenic Alzheimer's disease models.Cell reports · 2024Article
- Endothelial Dysfunctions in Blood-Brain Barrier Breakdown in Alzheimer's Disease: From Mechanisms to Potential Therapies.CNS neuroscience & therapeutics · 2024Review
- iPSC-derived blood-brain barrier modeling reveals APOE isoform-dependent interactions with amyloid beta.Fluids and barriers of the CNS · 2024Article
54 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Evidence indicates a critical role for cerebrovascular dysfunction in Alzheimer's disease (AD) pathophysiology. We have shown that fibrin(ogen), the principal blood-clotting protein, is deposited in the AD neurovasculature and interacts with beta-amyloid (Aβ), resulting in increased formation of blood clots. As apolipoprotein E (ApoE), a lipid-transporting protein with three human isoforms (E2, E3, and E4), also binds to Aβ, we hypothesized that ApoE and fibrin(ogen) may have a combined effect on the vascular pathophysiology in AD. We assessed whether APOE genotype differentially influences vascular fibrin(ogen) deposition in postmortem brain tissue using immunohistochemistry. An increased deposition of fibrin(ogen) was observed in AD cases compared with non-demented controls, and there was a strong correlation between cerebral amyloid angiopathy (CAA) severity and fibrin(ogen) deposition. Moreover, brains from AD cases homozygous for APOE ɛ4 showed increased deposition of fibrin(ogen), specifically in CAA- and oligomeric Aβ-positive vessels compared with AD APOE ɛ2 and ɛ3 allele carriers, an effect that was not directly linked to CAA severity and cerebrovascular atherosclerosis. These data further support a role for fibrin(ogen) in AD pathophysiology and link the APOE ɛ4/ɛ4 genotype with increased thrombosis and/or impaired fibrinolysis in the human AD brain.
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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.