β-Amyloid deposition in brain is enhanced in mouse models of arterial hypertension
β-Amyloid deposition in brain is enhanced in mouse models of arterial hypertension
复制标题
DOI：
10.1016/j.neurobiolaging.2007.06.005
复制
发表时间：
2009-02-01
影响因子：
4.2
通讯作者：
Lembo, Giuseppe
中科院分区：
文献类型：
--
作者：
Gentile, Maria Teresa;Poulet, Roberta;Lembo, Giuseppe
关于高血压与阿尔茨海默病（AD）之间的关联存在相互矛盾的证据，到目前为止，血压水平升高是否在机制上与AD的病理生理学相关仍未得到探究。由于β - 淀粉样蛋白（Aβ）在大脑中的沉积是AD发病的首要致病事件，在本研究中我们调查了高血压在Aβ大脑沉积中的作用。我们分析了两种独立的高血压小鼠模型。在这两种模型中，我们都观察到大脑皮质和海马区血脑屏障通透性增加。更有趣的是，在相同区域，高血压小鼠对抗Aβ抗体呈显著阳性，并且存在Aβ样片段。最后，我们分析了接受抗Aβ IgG被动免疫治疗后的小鼠。我们观察到后一种方法使大脑皮质和海马区的Aβ免疫阳性显著降低。我们的研究表明，慢性高血压会导致血脑屏障通透性受损，使Aβ在脑组织中沉积，而被动免疫治疗可阻止后一种现象。（C）2007爱思唯尔公司。保留所有权利。
There are conflicting evidence regarding the association of hypertension with Alzheimer's disease (AD), and so far it is still unexplored whether increased blood pressure levels can be mechanistically related to the pathophysiology of AD. since the deposition of beta-amyloid (A beta) in brain represents the first pathogenetic event in the onset of AD, in this Study we investigated the role of hypertension in the brain deposition of A beta. We analyzed two independent Mouse models of hypertension. In both models we observed an increased permeability of blood-brain barrier in cortex and hippocampus. More interestingly, in the same areas hypertensive mice showed a marked positivity to anti-A beta antibodies and the presence of A beta-like fragments. Finally, we analyzed mice after passive immunotherapy with anti-A beta IgG. We observed that this latter approach determined a markedly reduced A beta immunopositivity in both cortex and hippocampus. Our study demonstrates that chronic hypertension determines an impairment of the blood-brain barrier permeability with deposition of A beta in brain tissue and that passive immunotherapy prevents this latter phenomenon. (C) 2007 Elsevier Inc. All rights reserved.