Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
J Neurochem. 2010 Nov;115(3):551-62. doi: 10.1111/j.1471-4159.2010.06978.x. Epub 2010 Sep 28.
There is increasing evidence that the incidence of Alzheimer's disease (AD) is significantly influenced by cardiovascular risk factors in association with a cluster of metabolic diseases including diabetes and atherosclerosis. The shared risk is also reflected in the dietary and lifestyle links to both metabolic disorders and AD-type cognitive dysfunction. Recent studies with genetic and diet-induced animal models have begun to illuminate convergent mechanisms and mediators between these two categories of disease conditions with distinct tissue-specific pathologies. Although it is clear that peripheral inflammation and insulin resistance are central to the pathogenesis of the disorders of metabolic syndrome, it seems that the same mechanisms are also in play across the blood-brain barrier that lead to AD-like molecular and cognitive changes. This review highlights these convergent mechanisms and discusses the role of cerebrovascular dysfunction as a conduit to brain emergence of these pathogenic processes that might also represent future therapeutic targets in AD in common with metabolic disorders.
越来越多的证据表明，阿尔茨海默病（AD）的发病率受到心血管危险因素的显著影响，这些危险因素与包括糖尿病和动脉粥样硬化在内的一系列代谢疾病有关。这种共同的风险也反映在饮食和生活方式与代谢紊乱和 AD 型认知功能障碍之间的联系上。最近的遗传和饮食诱导动物模型研究开始阐明这两种疾病类别的趋同机制和介导因素，它们具有不同的组织特异性病理。虽然很明显，外周炎症和胰岛素抵抗是代谢综合征发病机制的核心，但似乎同样的机制也在发挥作用，导致血脑屏障出现类似 AD 的分子和认知变化。这篇综述强调了这些趋同机制，并讨论了脑血管功能障碍作为这些致病过程在大脑中出现的途径的作用，这些过程也可能代表 AD 与代谢紊乱的共同治疗靶点。
