Department of Physical Therapy, Health Science University, 7187 Kodachi, Fujikawaguchiko-machi, Minamitsuru-gun, Yamanashi 401-0380, Japan.
Department of Endocrinology, Metabolism, and Hypertension Research, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, 1-1 Fukakusa Mukaihata-cho, Fushimi-ku, Kyoto 612-8555, Japan.
Int J Mol Sci. 2020 Mar 14;21(6):1992. doi: 10.3390/ijms21061992.
Cerebral amyloid angiopathy (CAA) is a cerebrovascular disease directly implicated in Alzheimer's disease (AD) pathogenesis through amyloid-β (Aβ) deposition, which may cause the development and progression of dementia. Despite extensive studies to explore drugs targeting Aβ, clinical benefits have not been reported in large clinical trials in AD patients or presymptomatic individuals at a risk for AD. However, recent studies on CAA and AD have provided novel insights regarding CAA- and AD-related pathogenesis. This work has revealed potential therapeutic targets, including Aβ drainage pathways, Aβ aggregation, oxidative stress, and neuroinflammation. The functional significance and therapeutic potential of bioactive molecules such as cilostazol and taxifolin have also become increasingly evident. Furthermore, recent epidemiological studies have demonstrated that serum levels of a soluble form of triggering receptor expressed on myeloid cells 2 (TREM2) may have clinical significance as a potential novel predictive biomarker for dementia incidence. This review summarizes recent advances in CAA and AD research with a focus on discussing future research directions regarding novel therapeutic approaches and predictive biomarkers for CAA and AD.
脑淀粉样血管病（Cerebral Amyloid Angiopathy，CAA）通过β淀粉样蛋白（Amyloid-β，Aβ）沉积直接参与阿尔茨海默病（Alzheimer's disease，AD）的发病机制，可能导致痴呆的发生和发展。尽管针对 Aβ 的药物进行了广泛的研究，但在 AD 患者或有 AD 风险的无症状个体的大型临床试验中，并未报告有临床获益。然而，最近关于 CAA 和 AD 的研究为 CAA 和 AD 相关发病机制提供了新的见解。这项工作揭示了潜在的治疗靶点，包括 Aβ 引流途径、Aβ 聚集、氧化应激和神经炎症。西洛他唑和松脂素等生物活性分子的功能意义和治疗潜力也变得越来越明显。此外，最近的流行病学研究表明，髓样细胞表达的触发受体 2（Triggering Receptor Expressed on Myeloid Cells 2，TREM2）的一种可溶性形式的血清水平可能具有临床意义，作为痴呆发病的潜在新型预测生物标志物。本综述总结了 CAA 和 AD 研究的最新进展，重点讨论了针对 CAA 和 AD 的新型治疗方法和预测生物标志物的未来研究方向。
