阿迪波内克缺乏导致脑血管功能障碍,并与粉样蛋白-β协同作用,加剧阿尔茨海默氏症的病理
Wenying Zou1,2, Leung-Wah Yick1,2, Jason Shing-Cheong Kwan1,2
1Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
Alzheimer's research & therapy
|January 30, 2026
概括
在阿尔茨海默氏病 (AD) 模型中,阿迪波涅丁 (APN) 缺乏会使大脑血管功能障碍 (CVD) 恶化. 服用 APN 恢复了大脑血流和血脑屏障的完整性,这表明 APN 是阿尔茨海默病的潜在治疗目标.
科学领域:
- 神经科学是一个神经科学.
- 血管生物学 血管生物学
- 内分泌学 在内分泌学.
背景情况:
- 脑血管功能障碍 (CVD) 越来越多地与阿尔茨海默氏症 (AD) 病原发生有关.
- 阿迪波涅丁 (APN) 是一种具有外周血管保护作用的激素,在AD相关的脑血管健康中起着未知的作用.
- 了解APN对大脑血管系统的影响对于开发新型AD疗法至关重要.
研究的目的:
- 在阿尔茨海默氏病 (AD) 背景下,研究阿迪波涅丁 (APN) 在调节脑血管完整性方面的作用.
- 为了确定APN缺乏是否会加剧AD相关的心血管疾病.
- 评估APN在AD模型中恢复大脑血管功能的治疗潜力.
主要方法:
- 使用缺乏APN的小鼠和5xFAD转基因小鼠 (AD模型) 来评估心血管疾病标志物.
- 测量脑血流 (CBF) 和神经血管合 (NVC).
- 分析了血脑屏障 (BBB) 完整性,大脑粉样血管病变 (CAA) 和内皮细胞 (EC) 转录组学. 研究了APN对暴露于粉样β (Aβ) 的初级ECs的影响.
主要成果:
- 在小鼠中,APN缺乏导致CBF减少,NVC受损,BBB中断,CAA增强.
- 与单独使用5xFAD小鼠相比,缺乏APN的5xFAD小鼠表现出更严重的心血管疾病.
- 在5xFAD小鼠中,APN的使用逆转了CBF和NVC缺陷,并保护了初级ECs免受Aβ诱导的屏障破坏.
结论:
- 阿迪波涅丁 (APN) 在维持脑血管完整性方面起着至关重要的作用,特别是在阿尔茨海默病 (AD) 的背景下.
- 缺乏APN会加剧与AD相关的脑血管功能障碍 (CVD).
- 用APN准内皮细胞 (ECs) 是一个有前途的治疗策略,通过治疗心血管疾病来缓解AD的进展.
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