Alzheimer's disease peptide β-amyloid interacts with fibrinogen and induces its oligomerization
Alzheimer's disease peptide β-amyloid interacts with fibrinogen and induces its oligomerization
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DOI：
10.1073/pnas.1010373107
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发表时间：
2010-12-14
影响因子：
11.1
通讯作者：
Strickland, Sidney
中科院分区：
文献类型：
--
作者：
Ahn, Hyung Jin;Zamolodchikov, Daria;Strickland, Sidney
越来越多的证据支持血管对阿尔茨海默病（AD）的贡献，但AD和循环系统之间的直接联系尚未建立。先前的工作已经表明，在与AD有关的β-淀粉样肽（A β）存在下形成的血凝块具有异常结构，并且在体外和体内对降解具有抗性。在本研究中，我们发现A β与纤维蛋白原特异性相互作用，Kd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A β和纤维蛋白原之间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。总体而言，我们的研究表明，A β和纤维蛋白原之间的相互作用可能是AD中发现的血管异常的重要因素。
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.