Impaired Aβ clearance: a potential link between atherosclerosis and Alzheimer's disease.
Impaired Aβ clearance: a potential link between atherosclerosis and Alzheimer's disease.
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DOI：
10.3389/fnagi.2015.00115
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发表时间：
2015
影响因子：
4.8
通讯作者：
Iadecola C
中科院分区：
文献类型：
--
作者：
Gupta A;Iadecola C
阿尔茨海默病（AD）和动脉粥样硬化仍然是当今世界上两个最大的公共卫生负担。虽然传统上认为是不同的病理实体，越来越多的流行病学，临床和实验证据表明，脑血管粥样硬化和AD相互作用，破坏大脑结构和功能。而脑血管动脉粥样硬化引起的低灌注和缺氧可能会增加淀粉样β肽（Aβ）的产生，Aβ是AD病理学的核心肽，反过来，Aβ可能会通过血管氧化应激和内皮功能障碍促进动脉粥样硬化病变的形成，导致额外的血管损伤。在此，我们简要回顾了提示Aβ清除障碍是AD和脑血管疾病可能存在因果关系的额外、同时发生的机制的证据。我们检查了支持以下机制的文献：血流限制性大动脉狭窄、动脉硬化和微血管功能障碍可能通过损害Aβ清除率和升高脑Aβ水平而导致AD病理生理学。最后，我们强调需要进一步研究，以提高我们对AD和动脉粥样硬化与Aβ清除的复杂相互作用的理解，这可能最终有助于指导这种毁灭性和高度流行的疾病的新诊断和治疗方法的开发。
Alzheimer’s Disease (AD) and atherosclerosis remain two of the largest public health burdens in the world today. Although traditionally considered distinct pathological entities, mounting epidemiologic, clinical and experimental evidence suggests that cerebrovascular atherosclerosis and AD interact reciprocally to disrupt brain structure and function. Whereas the hypoperfusion and hypoxia caused by atherosclerosis of cerebral vessels may enhance the production of amyloid-β peptide (Aβ), a peptide central to AD pathology, Aβ, in turn, may promote formation of atherosclerotic lesions through vascular oxidative stress and endothelial dysfunction leading to additional vascular damage. Here, we briefly review evidence suggesting that impaired clearance of Aβ is an additional, simultaneously occurring mechanism by which AD and cerebrovascular disease may be causally linked. We examine the literature supporting mechanisms by which flow-limiting large-artery stenosis, arterial stiffening and microvascular dysfunction could contribute to AD pathophysiology by impairing Aβ clearance and elevating brain levels of Aβ. Finally, we highlight the need for further research to improve our understanding of the complex interactions of AD and atherosclerosis with Aβ clearance, which may ultimately serve to guide the development of novel diagnostic and therapeutic approaches for this devastating and highly prevalent condition.