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

Marta Cortes-Canteli, Justin Paul, Erin H. Norris, Robert Bronstein, Hyung Jin Ahn, Daria Zamolodchikov, Shivaprasad Bhuvanendran, Katherine M. Fenz, Sidney Strickland

Research output: Contribution to journalArticlepeer-review

177 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)695-709
Number of pages15
JournalNeuron
Volume66
Issue number5
DOIs
StatePublished - Jun 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Keywords

  • Cellbio
  • Humdisease
  • Molneuro

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