Fibrinogen and beta-amyloid association alters thrombosis and fibrinolysis: a possible contributing factor to Alzheimer's disease.
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.
Cortes-Canteli
Marta
M
Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, NY 10065, USA.
Paul
Justin
J
Norris
Erin H
EH
Bronstein
Robert
R
Ahn
Hyung Jin
HJ
Zamolodchikov
Daria
D
Bhuvanendran
Shivaprasad
S
Fenz
Katherine M
KM
Strickland
Sidney
S
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001777:Blood Coagulation / Q000235:genetics; D005340:Fibrinogen / Q000378:metabolism*; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D020767:Intracranial Thrombosis / Q000378:metabolism* / Q000503:physiopathology* / Q000517:prevention & control; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D005340:Fibrinogen