Alzheimer's disease peptide β-amyloid interacts with fibrinogen and induces its oligomerization

Increasing evidence supports a vascular contribution to Alzheimer's disease (AD), but a direct connection between AD and the circulatory system has not been established. Previous work has shown that blood clots formed in the presence of the beta-amyloid peptide (A beta), which has been implicated in AD, have an abnormal structure and are resistant to degradation in vitro and in vivo. In the present study, we show that A beta specifically interacts with fibrinogen with a K-d of 26.3 +/- 6.7 nM, that the binding site is located near the C terminus of the fibrinogen beta-chain, and that the binding causes fibrinogen to oligomerize. These results suggest that the interaction between A beta and fibrinogen modifies fibrinogen's structure, which may then lead to abnormal fibrin clot formation. Overall, our study indicates that the interaction between A beta and fibrinogen may be an important contributor to the vascular abnormalities found in AD.