Imaging of cerebrovascular pathology in animal models of Alzheimer's disease.
Imaging of cerebrovascular pathology in animal models of Alzheimer's disease.
复制标题
DOI：
10.3389/fnagi.2014.00032
复制
发表时间：
2014
影响因子：
4.8
通讯作者：
Beckmann N
中科院分区：
文献类型：
--
作者：
Klohs J;Rudin M;Shimshek DR;Beckmann N
在阿尔茨海默病(AD)中，血管病变可能与神经退行性变相互作用，从而加剧认知能力的下降。由于这两个过程之间的关系知之甚少，研究越来越多地集中在了解脑血管变化和AD之间的联系。这最终受到转基因动物工程的刺激，转基因动物表现出阿尔茨海默病的病理特征，并出现不同程度的脑淀粉样血管病变。转基因模型可用于研究淀粉样蛋白沉积和血管功能障碍的作用，以及评估新的治疗概念。此外，研究还得益于新的成像技术的发展，这些技术能够在体内表征血管病理。它们提供血管结构读数，并有能力评估血管功能障碍的功能后果，以及可视化和监测这些病理变化背后的分子过程。这篇文章集中于最近的活体小动物成像研究，解决与AD相关的血管方面的问题。随着磁共振、核成像和显微成像等成像技术的进步，与血管病理相关的分子、功能和结构信息现在可以在小啮齿动物体内可视化。成像血管和实质淀粉样蛋白(Aβ，Aβ)沉积以及Aβ转运通路有助于描述其动力学特征，并阐明其在脑淀粉样血管病和AD发生发展中的作用。结构和功能成像读数已经被用来描述Aβ对血管形态、血流动力学和血管完整性的有害影响。最近的影像研究也讨论了炎症过程如何参与疾病的发病机制。此外，在寻找针对血管系统的新疗法方面，成像可以起到关键作用。
In Alzheimer's disease (AD), vascular pathology may interact with neurodegeneration and thus aggravate cognitive decline. As the relationship between these two processes is poorly understood, research has been increasingly focused on understanding the link between cerebrovascular alterations and AD. This has at last been spurred by the engineering of transgenic animals, which display pathological features of AD and develop cerebral amyloid angiopathy to various degrees. Transgenic models are versatile for investigating the role of amyloid deposition and vascular dysfunction, and for evaluating novel therapeutic concepts. In addition, research has benefited from the development of novel imaging techniques, which are capable of characterizing vascular pathology in vivo. They provide vascular structural read-outs and have the ability to assess the functional consequences of vascular dysfunction as well as to visualize and monitor the molecular processes underlying these pathological alterations. This article focusses on recent in vivo small animal imaging studies addressing vascular aspects related to AD. With the technical advances of imaging modalities such as magnetic resonance, nuclear and microscopic imaging, molecular, functional and structural information related to vascular pathology can now be visualized in vivo in small rodents. Imaging vascular and parenchymal amyloid-β (Aβ) deposition as well as Aβ transport pathways have been shown to be useful to characterize their dynamics and to elucidate their role in the development of cerebral amyloid angiopathy and AD. Structural and functional imaging read-outs have been employed to describe the deleterious affects of Aβ on vessel morphology, hemodynamics and vascular integrity. More recent imaging studies have also addressed how inflammatory processes partake in the pathogenesis of the disease. Moreover, imaging can be pivotal in the search for novel therapies targeting the vasculature.