抗雄激素剥夺疗法通过增加大脑免疫细胞透加剧了与阿尔茨海默氏症相关的认知衰退
Chao Zhang1, Mae Aida2, Shalini Saggu2
1Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Science advances
|June 21, 2024
概括
前列腺癌的雄激素剥夺疗法 (ADT) 通过引起大脑炎症增加了痴呆症的风险. 纳塔利祖马布药物可以通过向免疫细胞来减少这种认知衰退.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
背景情况:
- 前列腺癌的雄激素剥夺疗法 (ADT) 与更高的痴呆风险有关,包括阿尔茨海默病 (AD).
- 连接ADT与前列腺癌患者认知障碍的确切机制尚未完全理解.
- 现有的研究往往侧重于粉样蛋白病理,可能会忽视其他有助于的因素.
研究的目的:
- 在前列腺癌小鼠模型中研究ADT和认知缺陷之间的机制联系.
- 探索免疫和炎症反应在ADT诱导的神经退行症中的作用.
- 评估纳塔利祖马布在缓解ADT相关认知障碍方面的治疗潜力.
主要方法:
- 用ADT开发一个临床相关的前列腺癌小鼠模型.
- 分析周围血液和脑组织中的免疫和炎症变化.
- 血脑屏障 (BBB) 完整性和免疫细胞透的评估.
- 对认知功能和神经炎症标志物的评估.
- 测试纳塔利祖马布治疗的疗效.
主要成果:
- ADT和前列腺瘤诱导了显著的免疫和炎症变化.
- ADT破坏了BBB的完整性,导致免疫细胞透和神经炎症的增加.
- 神经炎症和结症增强,独立于粉样质斑块负载.
- 在模型中,natalizumab治疗减少了神经炎症,并改善了认知功能.
结论:
- ADT通过一种与粉样蛋白病理学不同的炎症机制加剧认知缺陷.
- 免疫细胞透到大脑在ADT诱导的神经炎症中起着关键作用.
- 纳塔利祖马布作为一种治疗剂,有望抵消ADT对认知的负面影响.
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