Dementia Research Group, Translational Health Sciences, Bristol Medical School, University of Bristol, Southmead Hospital, Bristol, UK.
J Alzheimers Dis. 2018;62(3):1443-1466. doi: 10.3233/JAD-171119.
There is wide recognition of a complex association between midlife hypertension and cardiovascular disease and later development of Alzheimer's disease (AD) and cognitive impairment. While significant progress has been made in reducing rates of mortality and morbidity due to cardiovascular disease over the last thirty years, progress towards effective treatments for AD has been slower. Despite the known association between hypertension and dementia, research into each disease has largely been undertaken in parallel and independently. Yet over the last decade and a half, the emergence of converging findings from pre-clinical and clinical research has shown how the renin angiotensin system (RAS), which is very important in blood pressure regulation and cardiovascular disease, warrants careful consideration in the pathogenesis of AD. Numerous components of the RAS have now been found to be altered in AD such that the multifunctional and potent vasoconstrictor angiotensin II, and similarly acting angiotensin III, are greatly altered at the expense of other RAS signaling peptides considered to contribute to neuronal and cognitive function. Collectively these changes may contribute to many of the neuropathological hallmarks of AD, as well as observed progressive deficiencies in cognitive function, while also linking elements of a number of the proposed hypotheses for the cause of AD. This review discusses the emergence of the RAS and its likely importance in AD, not only because of the multiple facets of its involvement, but also perhaps fortuitously because of the ready availability of numerous RAS-acting drugs, that could be repurposed as interventions in AD.
人们普遍认识到，中年高血压与心血管疾病之间存在复杂的关联，而心血管疾病与阿尔茨海默病（AD）和认知障碍的后期发展也存在关联。尽管在过去三十年中，在降低心血管疾病死亡率和发病率方面取得了重大进展，但 AD 有效治疗方法的进展较为缓慢。尽管高血压和痴呆之间存在已知的关联，但针对这两种疾病的研究在很大程度上是并行和独立进行的。然而，在过去的十五年中，来自临床前和临床研究的趋同发现表明，肾素-血管紧张素系统（RAS）在血压调节和心血管疾病中非常重要，值得在 AD 的发病机制中仔细考虑。现在已经发现，AD 中 RAS 的许多成分发生了改变，因此多功能且强效的血管收缩素 II 和具有类似作用的血管紧张素 III 发生了极大的改变，而其他被认为有助于神经元和认知功能的 RAS 信号肽则减少。这些变化可能导致 AD 的许多神经病理学特征，以及观察到的认知功能逐渐下降，同时也将 AD 一些假设病因的元素联系起来。本文综述了 RAS 的出现及其在 AD 中的可能重要性，不仅因为其涉及的多个方面，还因为大量具有 RAS 作用的药物已经上市，这些药物可能被重新用于 AD 的干预治疗。
