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

被引：273

作者：

Cortes-Canteli, Marta ^{[1
]}

Paul, Justin ^{[1
]}

Norris, Erin H. ^{[1
]}

Bronstein, Robert ^{[1
]}

Ahn, Hyung Jin ^{[1
]}

Zamolodchikov, Daria ^{[1
]}

Bhuvanendran, Shivaprasad ^{[2
]}

Fenz, Katherine M. ^{[1
]}

Strickland, Sidney ^{[1
]}

机构：

[1] Rockefeller Univ, Lab Neurobiol & Genet, New York, NY 10065 USA

[2] Rockefeller Univ, Bioimaging Resource Ctr, New York, NY 10065 USA

来源：

NEURON | 2010年 / 66卷 / 05期

基金：

美国国家卫生研究院;

关键词：

BLOOD-BRAIN-BARRIER; MILD COGNITIVE IMPAIRMENT; TISSUE-PLASMINOGEN-ACTIVATOR; TRANSGENIC MICE; RISK-FACTORS; ANTICOAGULANT-THERAPY; ATRIAL-FIBRILLATION; VASCULAR DISORDER; PLAQUE-FORMATION; DEFICIENT MICE;

D O I：

10.1016/j.neuron.2010.05.014

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Alzheimer's disease (AD) is a neurodegenerative disorder in which vascular pathology plays an important role. Since the beta-amyloid peptide (A beta) 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 A beta 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 A beta to AD is via its effects on fibrin clots, implicating fibrin(ogen) as a potential critical factor in this disease.

引用

页码：695 / 709

页数：15

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