Key points class="unordered" style="list-style-type:disc" id="tjp7307-list-0001">Hyperfibrinogenaemia (HFg) results in vascular remodelling, and fibrinogen (Fg) and amyloid β (Aβ) complex formation is a hallmark of Alzheimer's disease. However, the interconnection of these effects, their mechanisms and implications in cerebrovascular diseases are not known.Using a mouse model of HFg, we showed that at an elevated blood level, Fg increases cerebrovascular permeability via mainly caveolar protein transcytosis.This enhances deposition of Fg in subendothelial matrix and interstitium making the immobilized Fg a readily accessible substrate for binding Aβ and cellular prion protein (PrPC), the protein that is thought to have a greater effect on memory than Aβ.We showed that enhanced formation of Fg–Aβ and Fg–PrPC complexes are associated with reduction in short‐term memory.The present study delineates a new mechanistic pathway for vasculo‐neuronal dysfunctions found in inflammatory cardiovascular and cerebrovascular diseases associated with an elevated blood level of Fg.
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机译：关键点 class =“ unordered” style =“ list-style-type：disc” id =“ tjp7307-list-0001”> <！-list-behavior = unordered prefix-word = mark-type = disc max- label-size = 0-> li>高纤维蛋白原血症（HFg）导致血管重塑，而纤维蛋白原（Fg）和淀粉样β（Aβ）复合物的形成是阿尔茨海默氏病的标志。但是，这些作用的相互关系，其作用机制及其在脑血管疾病中的作用尚不清楚。 使用HFg小鼠模型，我们发现在血药水平升高时，Fg主要通过海绵体蛋白增加了脑血管通透性 这增强了Fg在内皮下基质和间质中的沉积，使固定的Fg成为结合Aβ和细胞病毒蛋白（PrP C ）的容易获得的底物。 我们证明Fg–Aβ和Fg–PrP C 复合物形成的增强与短期记忆的减少有关。 本研究描述了与Fg升高相关的炎性心血管疾病和脑血管疾病中发现的血管神经元功能异常的新机制。
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