Saito Satoshi, Tanaka Masashi, Satoh-Asahara Noriko, Carare Roxana Octavia, Ihara Masafumi
Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan.
Front Pharmacol. 2021 Feb 12;12:643357. doi: 10.3389/fphar.2021.643357. eCollection 2021.
Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of β-amyloid (Aβ) in the walls of cerebral vessels, leading to complications such as intracerebral hemorrhage, convexity subarachnoid hemorrhage and cerebral microinfarcts. Patients with CAA-related intracerebral hemorrhage are more likely to develop dementia and strokes. Several pathological investigations have demonstrated that more than 90% of Alzheimer's disease patients have concomitant CAA, suggesting common pathogenic mechanisms. Potential causes of CAA include impaired Aβ clearance from the brain through the intramural periarterial drainage (IPAD) system. Conversely, CAA causes restriction of IPAD, limiting clearance. Early intervention in CAA could thus prevent Alzheimer's disease progression. Growing evidence has suggested Taxifolin (dihydroquercetin) could be used as an effective therapy for CAA. Taxifolin is a plant flavonoid, widely available as a health supplement product, which has been demonstrated to exhibit anti-oxidative and anti-inflammatory effects, and provide protection against advanced glycation end products and mitochondrial damage. It has also been shown to facilitate disassembly, prevent oligomer formation and increase clearance of Aβ in a mouse model of CAA. Disturbed cerebrovascular reactivity and spatial reference memory impairment in CAA are completely prevented by Taxifolin treatment. These results highlight the need for clinical trials on the efficacy and safety of Taxifolin in patients with CAA.
脑淀粉样血管病(CAA)的特征是脑血管壁中β淀粉样蛋白(Aβ)的积累,导致脑出血、脑凸面蛛网膜下腔出血和脑微梗死等并发症。患有CAA相关性脑出血的患者更有可能发展为痴呆和中风。多项病理学研究表明,超过90%的阿尔茨海默病患者同时患有CAA,提示存在共同的致病机制。CAA的潜在病因包括通过壁内动脉周围引流(IPAD)系统从脑中清除Aβ受损。相反,CAA会导致IPAD受限,限制清除。因此,对CAA的早期干预可以预防阿尔茨海默病的进展。越来越多的证据表明,紫杉叶素(二氢槲皮素)可作为治疗CAA的有效疗法。紫杉叶素是一种植物类黄酮,作为一种健康补充产品广泛可得,已被证明具有抗氧化和抗炎作用,并能保护机体免受晚期糖基化终产物和线粒体损伤。在CAA小鼠模型中,它还被证明能促进Aβ的分解、防止寡聚体形成并增加其清除。紫杉叶素治疗可完全预防CAA中脑血管反应性紊乱和空间参考记忆障碍。这些结果凸显了对紫杉叶素治疗CAA患者的疗效和安全性进行临床试验的必要性。