Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, NY 10065, USA.
Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21812-7. doi: 10.1073/pnas.1010373107. Epub 2010 Nov 22.
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 β-amyloid peptide (Aβ), 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 Aβ 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 β-chain, and that the binding causes fibrinogen to oligomerize. These results suggest that the interaction between Aβ and fibrinogen modifies fibrinogen's structure, which may then lead to abnormal fibrin clot formation. Overall, our study indicates that the interaction between Aβ and fibrinogen may be an important contributor to the vascular abnormalities found in AD.
越来越多的证据支持血管因素与阿尔茨海默病（AD）有关，但 AD 与循环系统之间的直接联系尚未建立。先前的研究表明，在β-淀粉样肽（Aβ）存在的情况下形成的血栓具有异常的结构，并且在体外和体内都不易降解。在本研究中，我们表明 Aβ 与纤维蛋白原特异性结合，K(d)值为 26.3 ± 6.7 nM，结合位点位于纤维蛋白原β链的 C 末端附近，并且结合导致纤维蛋白原寡聚化。这些结果表明 Aβ 与纤维蛋白原的相互作用改变了纤维蛋白原的结构，这可能导致异常的纤维蛋白凝块形成。总的来说，我们的研究表明，Aβ 与纤维蛋白原的相互作用可能是 AD 中血管异常的一个重要因素。
