在TMEM106B中的遗传变异改变了慢性创伤性脑病变中的微质激活和细胞因子反应
Shahar Hartman1, Nurgul Aytan1,2, Raymond Nicks1,2,3,4
1Boston University Alzheimer's Disease Research Center and CTE Center, Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, USA.
Acta neuropathologica
|November 20, 2025
概括
一种特定的基因变异 (TMEM106B rs3173615) 增加了慢性创伤性脑病变 (CTE) 的风险和严重程度. 这种遗传因素影响炎症反应和微质激活,导致CTE病理.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 遗传学 是一个
- 免疫学 免疫学 免疫学
背景情况:
- 慢性创伤性脑病 (CTE) 是一种神经退行性疾病,与重复的头部冲击 (RHI) 有关.
- 个体对CTE的敏感性尽管具有相似的RHI暴露,但仍有所不同,这表明存在遗传因素.
- 已知跨膜蛋白106B (TMEM106B) 基因的风险变异与CTE严重程度的增加有关,但其机制尚未完全理解.
研究的目的:
- 研究TMEM106B风险变体 (rs3173615) 在CTE内的炎症反应中的作用.
- 检查TMEM106B基因型,微质激活,炎症性细胞因子和CTE的神经病理特征之间的关联.
- 确定TMEM106B基因型是否影响炎症标志物和CTE相关病理之间的关系.
主要方法:
- 对323名暴露于RHI的大脑捐赠者的分析,包括对照组和患有CTE的人.
- 免疫组织化学评估微质和免疫测试来测量炎症性细胞因子.
- 回归模型测试TMEM106B风险基因型与CTE阶段,TDP-43病理和痴呆症之间的关联,按年龄分层.
主要成果:
- 在65岁以上的个体中,TMEM106B风险基因型与增加的CTE阶段和更高的TDP-43含入率相关.
- 在65岁及以下的个体中,TMEM106B风险基因型与更高的痴呆率有关.
- TMEM106B基因型显著影响了炎症标志物 (细胞因子) 和CTE病理之间的关系,在风险基因型中观察到异常关联.
结论:
- TMEM106B rs3173615风险变体与更高的CTE阶段和TDP-43病理有关,特别是在老年人中.
- 这种遗传变异可能会增加RHI暴露的年轻个体的痴呆风险.
- 在存在TMEM106B风险基因型的情况下,异常的微质激活和细胞因子的产生可能会导致CTE的发病.
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