脑淀粉样血管病疾病修饰治疗研究进展

Research progress in the disease-modifing therapy of cerebral amyloid angiopathy

脑淀粉样血管病(CAA)的机制尚未完全阐明,β淀粉样蛋白(Aβ)的产生-清除平衡失调引起Aβ沉积及其后续的氧化应激、炎症反应是血管壁破坏的关键环节。目前对CAA的治疗集中于出血事件的防治、对症治疗,而关于防止疾病进展的疾病修饰治疗尚无实质性成果。基于CAA可能的发病机制,前期已发现多个有望改善预后及临床结局的治疗靶点,包括减少Aβ产生、免疫介导的Aβ清除、增加Aβ生理性清除、抗氧化及抗炎等,部分靶点已有临床研究证据支撑,大部分研究仍处于临床前阶段,今后对CAA疾病修饰治疗的进一步基础和临床研究具有重要的临床意义。

The mechanism of cerebral amyloid angiopathy (CAA) has not been fully elucidated. The imbalance between the production and clearance of amyloid β (Aβ) leads to the deposition of Aβ and subsequent oxidative stress and inflammatory responses, which are key factors in the destruction of the vascular wall. Current treatments for CAA focus on the preventing and providing symptomatic treatment of hemorrhages while there has been no substantial progress in disease-modifying therapies to prevent disease progression. Based on the possible pathogenesis of CAA, several potential therapeutic targets have been identified that could improve prognosis and clinical outcomes, including reducing Aβ production, immune-mediated Aβ clearance, increasing physiological Aβ clearance, and anti-oxidation and anti-inflammatory measures. Some targets are supported by clinical research evidence, while most research remains still in the preclinical stage. Further basic and clinical research on disease-modifying therapies for CAA is of significant clinical importance.