Bonnar Orla, Eyre Beth, van Veluw Susanne J
MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Neurotherapeutics. 2025 Apr;22(3):e00535. doi: 10.1016/j.neurot.2025.e00535. Epub 2025 Jan 30.
Although distinct diseases, both cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD) are characterized by the aggregation and accumulation of amyloid-β (Aβ). This is thought to be due, in part, to impaired perivascular Aβ clearance from the brain. This shared failure in both diseases presents a common opportunity for therapeutic intervention. In this review we discuss the idea that promoting perivascular brain clearance could be an effective strategy for safely reducing Aβ levels in CAA and AD thereby improving clinical outcomes, most notably hemorrhagic stroke and cognitive decline. We will explore the evidence for the different forces that are thought to drive perivascular brain clearance, review the literature on potential strategies for potentiating these driving forces, and finally we will discuss the substantial translational challenges and considerations that would accompany such an intervention.
尽管脑淀粉样血管病（CAA）和阿尔茨海默病（AD）是不同的疾病，但它们都以淀粉样β蛋白（Aβ）的聚集和积累为特征。部分原因被认为是脑内血管周围Aβ清除受损。这两种疾病中这种共同的功能障碍为治疗干预提供了一个共同的契机。在这篇综述中，我们讨论了促进血管周围脑清除可能是一种有效策略的观点，即安全降低CAA和AD中的Aβ水平，从而改善临床结局，最显著的是出血性中风和认知衰退。我们将探讨被认为驱动血管周围脑清除的不同力量的证据，回顾关于增强这些驱动力的潜在策略的文献，最后我们将讨论这种干预所伴随的重大转化挑战和考量因素。
