Cerebral amyloid angiopathy and Alzheimer disease - one peptide, two pathways.,Nature Reviews Neurology

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Cerebral amyloid angiopathy and Alzheimer disease - one peptide, two pathways.
Nature Reviews Neurology ( IF 28.2 ) Pub Date : 2019-12-11 , DOI: 10.1038/s41582-019-0281-2
Steven M Greenberg ₁ , Brian J Bacskai ₁ , Mar Hernandez-Guillamon ₂ , Jeremy Pruzin ₃ , Reisa Sperling ₃ , Susanne J van Veluw ₁

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The shared role of amyloid-β (Aβ) deposition in cerebral amyloid angiopathy (CAA) and Alzheimer disease (AD) is arguably the clearest instance of crosstalk between neurodegenerative and cerebrovascular processes. The pathogenic pathways of CAA and AD intersect at the levels of Aβ generation, its circulation within the interstitial fluid and perivascular drainage pathways and its brain clearance, but diverge in their mechanisms of brain injury and disease presentation. Here, we review the evidence for and the pathogenic implications of interactions between CAA and AD. Both pathologies seem to be driven by impaired Aβ clearance, creating conditions for a self-reinforcing cycle of increased vascular Aβ, reduced perivascular clearance and further CAA and AD progression. Despite the close relationship between vascular and plaque Aβ deposition, several factors favour one or the other, such as the carboxy-terminal site of the peptide and specific co-deposited proteins. Amyloid-related imaging abnormalities that have been seen in trials of anti-Aβ immunotherapy are another probable intersection between CAA and AD, representing overload of perivascular clearance pathways and the effects of removing Aβ from CAA-positive vessels. The intersections between CAA and AD point to a crucial role for improving vascular function in the treatment of both diseases and indicate the next steps necessary for identifying therapies.

中文翻译：

脑淀粉样血管病和阿尔茨海默病 - 一种肽，两种途径。

β淀粉样蛋白（Aβ）沉积在脑淀粉样血管病（CAA）和阿尔茨海默病（AD）中的共同作用可以说是神经退行性和脑血管过程之间串扰的最明显实例。 CAA和AD的致病途径在Aβ生成、其在间质液内的循环和血管周围引流途径及其脑清除水平上相交，但在脑损伤和疾病表现的机制上有所不同。在这里，我们回顾了 CAA 和 AD 之间相互作用的证据及其致病影响。这两种病理似乎都是由 Aβ 清除受损驱动的，为血管 Aβ 增加、血管周围清除减少以及 CAA 和 AD 进一步进展的自我强化循环创造了条件。尽管血管和斑块 Aβ 沉积之间存在密切关系，但有几个因素有利于其中之一，例如肽的羧基末端位点和特定的共沉积蛋白质。抗 Aβ 免疫疗法试验中发现的淀粉样蛋白相关成像异常是 CAA 和 AD 之间的另一个可能的交叉点，代表血管周围清除途径的过载以及从 CAA 阳性血管中去除 Aβ 的影响。 CAA 和 AD 之间的交叉点表明改善血管功能在这两种疾病的治疗中发挥着至关重要的作用，并指出了确定治疗方法所需的后续步骤。

更新日期：2019-12-11

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