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

• DOI: 10.1016/j.neuron.2010.05.014
• Publication Date: 2010-06-11T11:03:08Z
• Authors: Marta Cortes-Canteli; Justin Paul; Erin H. Norris; Robert Bronstein; Hyung Jin Ahn; Daria Zamolodchikov; Shivaprasad Bhuva...; Katherine M. Fenz; Sidney Strickland
• Keywords: Aged, 80 and over; Mice, Inbred C3H; Amyloid beta-Peptides; Neuroscience(all); Fibrinolysis; HUMDISEASE; Fibrinogen; Mice, Transgenic; Middle Aged; MOLNEURO; Peptide Fragments; 3. Good health; Mice, Inbred C57BL; Mice; Alzheimer Disease; Animals; Humans; CELLBIO; Intracranial Thrombosis; Blood Coagulation; Aged; Protein Binding

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.