Neuroinflammation as a mechanism linking hypertension with the increased risk of Alzheimer's disease.
Neuroinflammation as a mechanism linking hypertension with the increased risk of Alzheimer's disease.
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DOI：
10.4103/1673-5374.336869
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发表时间：
2022-11
影响因子：
6.1
通讯作者：
Klegeris, Andis
中科院分区：
文献类型：
--
作者：
Bajwa, Ekta;Klegeris, Andis
关键词：
阿尔茨海默病是老年人中最常见的痴呆症，目前无法预防或有效治疗。只有很小比例的阿尔茨海默病病例有确定的遗传原因。大多数阿尔茨海默病病例缺乏明确的病因，但几个可改变的因素与这种疾病的风险增加有关。持续性中年高血压就是这样一个危险因素，可以通过改变饮食、生活方式和抗高血压药物来有效控制。确定将可改变的风险因素与阿尔茨海默病风险增加联系起来的分子机制可以增强我们对这种疾病的理解，并导致确定有效治疗的新靶点和治疗方法。胶质细胞驱动的神经炎症是阿尔茨海默病的关键病理特征之一。在这篇综述中，我们说明神经炎症也可能是高血压和阿尔茨海默病的可能机制之一。动物研究表明，长期血压升高会导致不良的胶质细胞激活和脑炎症介质增加。我们强调脑微血管损伤和局部激活的肾素-血管紧张素系统是连接高血压与神经炎症和伴随的神经退行性变的关键发病机制。肿瘤坏死因子-α和白细胞介素-1 β作为提供这种联系的促炎信号分子的作用进行了讨论。我们还总结了现有的实验数据表明，神经炎症变化和胶质细胞活化可以逆转几种不同类别的抗高血压药物。这些研究表明，抗高血压药物可能对阿尔茨海默病有益，不仅因为它们能够控制血压，而且还因为它们的抗神经炎症作用。在人类受试者中证实这些观察结果是必要的，并且脑成像技术的最新进展允许小胶质细胞和星形胶质细胞活化的可视化对于这项研究至关重要。
Alzheimer’s disease, the most common type of dementia among older adults, currently cannot be prevented or effectively treated. Only a very small percentage of Alzheimer’s disease cases have an established genetic cause. The majority of Alzheimer’s disease cases lack a clear causative event, but several modifiable factors have been associated with an increased risk of this disease. Persistent midlife hypertension is one such risk factor, which can be effectively controlled through changes in diet, lifestyle, and antihypertensive drugs. Identifying molecular mechanisms linking modifiable risk factors with the increased risk of Alzheimer’s disease could enhance our understanding of this disease and lead to identification of novel targets and therapeutic approaches for effective treatments. Glial cell-driven neuroinflammation is one of the key pathological features of Alzheimer’s disease. In this review, we illustrate that neuroinflammation could also be one of the possible mechanisms linking hypertension and Alzheimer’s disease. Animal studies have demonstrated that chronically elevated blood pressure leads to adverse glial activation and increased brain inflammatory mediators. We highlight damage to cerebral microvasculature and locally activated renin-angiotensin system as the key pathogenetic mechanisms linking hypertension to neuroinflammation and the accompanying neurodegeneration. The role of tumor necrosis factor-α and interleukin-1β as pro-inflammatory signaling molecules providing this link is discussed. We also summarize the available experimental data indicating that neuroinflammatory changes and glial activation can be reversed by several different classes of antihypertensive medicines. These studies suggest antihypertensives could be beneficial in Alzheimer’s disease not only due to their ability to control the blood pressure, but also due to their anti-neuroinflammatory effects. Confirmation of these observations in human subjects is required and recent advances in the brain imaging techniques allowing visualization of both microglia and astrocyte activation will be essential for this research.
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影响因子：
7.3
作者：
Alexander, Matthew R.;Norlander, Allison E.;Madhur, Meena S.
通讯作者：
Madhur, Meena S.
影响因子：
5.4
作者：
Denes A;Drake C;Stordy J;Chamberlain J;McColl BW;Gram H;Crossman D;Francis S;Allan SM;Rothwell NJ
通讯作者：
Rothwell NJ
影响因子：
4.2
作者：
Carnevale, Daniela;Mascio, Giada;Minghetti, Luisa
通讯作者：
Minghetti, Luisa
影响因子：
5.3
作者：
Fakhoury M
通讯作者：
Fakhoury M
影响因子：
48
作者：
Barnes, Deborah E.;Yaffe, Kristine
通讯作者：
Yaffe, Kristine