Fibrinogen and β-Amyloid Association Alters Thrombosis and Fibrinolysis: A Possible Contributing Factor to Alzheimer's Disease

Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, NY 10065, USA.
Neuron (Impact Factor: 15.05). 06/2010; 66(5):695-709. DOI: 10.1016/j.neuron.2010.05.014
Source: PubMed


Alzheimer's disease (AD) is a neurodegenerative disorder in which vascular pathology plays an important role. Since the beta-amyloid peptide (Abeta) is a critical factor in this disease, we examined its relationship to fibrin clot formation in AD. In vitro and in vivo experiments showed that fibrin clots formed in the presence of Abeta are structurally abnormal and resistant to degradation. Fibrin(ogen) was observed in blood vessels positive for amyloid in mouse and human AD samples, and intravital brain imaging of clot formation and dissolution revealed abnormal thrombosis and fibrinolysis in AD mice. Moreover, depletion of fibrinogen lessened cerebral amyloid angiopathy pathology and reduced cognitive impairment in AD mice. These experiments suggest that one important contribution of Abeta to AD is via its effects on fibrin clots, implicating fibrin(ogen) as a potential critical factor in this disease.

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Available from: Daria Zamolodchikov
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    • "Besides platelet hyper activation, coagulation is also impaired in AD patients. In particular it has been observed that Aβ is able to bind fibrinogen and that fibrin clot formed in the presence of Aβ are more stable and more resistant to degradation during fibrinolysis (Ahn et al., 2010; Cortes-Canteli et al., 2010). After BBB alterations fibrinogen may deposit to brain blood vessel and accumulate in CAA and parenchyma in AD patients, and in AD mouse models (Paul et al., 2007). "
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    • "To assess whether our lead compound could restore Ainduced altered thrombosis and fibrinolysis in vivo, we examined cerebral blood flow and thrombosis in a transgenic mouse model of AD, Tg6799 mice (Oakley et al., 2006), with or without long-term treatment of RU-505. Blood flow and thrombosis were analyzed by a FeCl 3 -induced thrombosis model combined with intravital microscopy (Cortes-Canteli et al., 2010). We administered RU-505 or vehicle (35 mg/kg dose, every other day) to 4-mo-old Tg6799 and WT littermates for 4 mo (analyzed at 8 mo of age). "
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    • "APP which includes complement components, are of interest and A aggregations involved complement activation in atherosclerosis and AD [192] [193]. In particular, convergence of the role of apo E in coronary artery disease is possibly related to the interactions of fibrinogen and A to promote fibrin clot formation and vascular abnormalities [194] [195]. "
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