Liaoning Provincial Center for Clinical Research on Neurological Diseases, The First Affiliated Hospital, Dalian Medical University, Dalian 116021, China.
Liaoning Provincial Key Laboratory for Research on the Pathogenic Mechanisms of Neurological Diseases, The First Affiliated Hospital, Dalian Medical University, Dalian 116021, China.
Aging (Albany NY). 2021 Sep 3;13(17):21791-21806. doi: 10.18632/aging.203482.
Alzheimer's disease (AD), as the most common neurodegenerative disease in elder population, is pathologically characterized by β-amyloid (Aβ) plaques, neurofibrillary tangles composed of highly-phosphorylated tau protein and consequently progressive neurodegeneration. However, both Aβ and tau fails to cover the whole pathological process of AD, and most of the Aβ- or tau-based therapeutic strategies are all failed. Increasing lines of evidence from both clinical and preclinical studies have indicated that age-related cerebrovascular dysfunctions, including the changes in cerebrovascular microstructure, blood-brain barrier integrity, cerebrovascular reactivity and cerebral blood flow, accompany or even precede the development of AD-like pathologies. These findings may raise the possibility that cerebrovascular changes are likely pathogenic contributors to the onset and progression of AD. In this review, we provide an appraisal of the cerebrovascular alterations in AD and the relationship to cognitive impairment and AD pathologies. Moreover, the adrenergic mechanisms leading to cerebrovascular and AD pathologies were further discussed. The contributions of early cerebrovascular factors, especially through adrenergic mechanisms, should be considered and treasured in the diagnostic, preventative, and therapeutic approaches to address AD.
阿尔茨海默病（AD）是最常见的老年人群神经退行性疾病，其病理特征为β-淀粉样蛋白（Aβ）斑块、由高度磷酸化的 tau 蛋白组成的神经原纤维缠结以及随后的进行性神经退行性变。然而，Aβ和 tau 都不能涵盖 AD 的整个病理过程，并且大多数基于 Aβ或 tau 的治疗策略都失败了。越来越多的临床和临床前研究证据表明，与年龄相关的脑血管功能障碍，包括脑血管微观结构、血脑屏障完整性、脑血管反应性和脑血流的变化，与 AD 样病理的发展相伴或甚至先于其发展。这些发现可能提示脑血管变化很可能是 AD 发病和进展的致病因素。在这篇综述中，我们评估了 AD 中的脑血管改变及其与认知障碍和 AD 病理的关系。此外，还进一步讨论了导致脑血管和 AD 病理的肾上腺素能机制。在 AD 的诊断、预防和治疗方法中，应考虑并重视早期脑血管因素的作用，尤其是通过肾上腺素能机制的作用。
