Activation of the contact system in cerebrospinal fluid of patients with Alzheimer disease
Activation of the contact system in cerebrospinal fluid of patients with Alzheimer disease
复制标题
DOI：
10.1097/00002093-199806000-00008
复制
发表时间：
1998-06-01
影响因子：
2.1
通讯作者：
Agostoni, A
中科院分区：
文献类型：
--
作者：
Bergamaschini, L;Parnetti, L;Agostoni, A
几条趋同的证据表明，β-淀粉样蛋白和炎症可能在阿尔茨海默病(AD)的发病机制中有关，但β-淀粉样蛋白神经毒性的机制尚不清楚，在本研究中，通过证明高分子激肽原可能在AD患者的脑脊液(CSF)中大量裂解，我们提供了接触系统可能参与本病炎症过程的证据。在神经免疫性炎症性疾病(多发性硬化症、慢性炎症性脱髓鞘多神经病)患者的脑脊液中，没有证据表明高分子激肽原裂解增加，提示这一发现可能是阿尔茨海默脑的特征。体外实验数据似乎表明，高分子量激肽原在体内的切割可能是β-淀粉样蛋白与XII因子相互作用和激肽释放酶生成的结果。这种现象的实际相关性仍有待在活体内确定。然而，阿尔茨海默病患者大脑中接触系统可能被激活的证据表明，激肽释放酶-激动素系统可能参与了这种疾病的炎症过程。
Several converging lines of evidence suggest that beta-amyloid and inflammation may be linked in the pathogenesis of Alzheimer disease (AD), but the mechanism of beta-amyloid neurotoxicity is unclear, in this study, by demonstrating that high molecular weight kininogen may be massively cleaved in the cerebrospinal fluid (CSF) of patients with AD, we provide evidence of the potential involvement of the contact system in the inflammatory processes taking place in this disease. In the CSF of patients with neuroimmune inflammatory disease (multiple sclerosis, chronic inflammatory demyelinating polyneuropathy), there was no evidence of increased cleavage of high molecular weight kininogen, suggesting that this finding maybe characteristic of the Alzheimer brain. The data obtained from in vitro experiments seem to indicate that the cleavage of high molecular weight kininogen in vivo may be the result of the interaction of beta-amyloid with factor XII and of kallikrein generation. The actual relevance of such a phenomenon remains to be established in vivo. However, the demonstration that the contact system may be activated in the brains of Alzheimer patients points to the potential involvement of the kallikrein-kinin system in the inflammatory process of this disease.