基础科学和病原发生学
Pablo Zaragoza-Ballester1,2,3, Briggitte Nuscher4,5, Daniel Alcolea6,7
1Nuclear Medicine Department, Hospital Universitario 12 de Octubre, Madrid, Madrid, Spain.
Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 23, 2025
概括
APOEε4载体降低了Lewy体 (DLB) 早期痴呆症的TREM2响应,但高水平的TREM2在prodromal DLB中与较慢的认知衰退相关,表明微质激活的保护作用.
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:
- APOEε4是已知的阿尔茨海默病 (AD) 和患有勒维体 (DLB) 的痴呆症的风险因素.
- 通过TREM2介导的微质激活与AD病变发生有关,并且可能与APOE相互作用.
- DLB经常呈现AD共病理,需要对DLB.内的这些相互作用进行调查.
研究的目的:
- 调查TREM2反应,APOEε4携带和DLB的AD共病学之间的相互作用.
- 确定这些因素如何影响DLB的进展.
- 检查微质激活在早期DLB中的作用.
主要方法:
- 测量的大脑脊髓液 (CSF) 在76名DLB患者 (前期DLB和DLB痴呆症) 中分裂的可溶性TREM2 (cTREM2).
- 评估的APOEε4载体和核心AD生物标志物 (Aβ42,t-tau,p-tau181).
- 在一小部分患者中利用[18F]Florbetapir-PET成像,并进行临床随访.
主要成果:
- 与非携带者相比,APOEε4携带者在prodromal DLB中显示出明显较低的cTREM2水平.
- 在prodromal DLB中较低的cTREM2水平与APOEε4携带独立相关.
- 预发性DLB中cTREM2水平升高与较高的AD生物标志物和较慢的认知衰退相关,而DLB-痴呆症中没有这种关联.
结论:
- APOEε4载体减弱了TREM2依赖的微质响应在前期的DLB.
- 在早期的DLB中,较高的cTREM2水平表明微质激活具有保护作用.
- 这些发现突出了APOEε4对TREM2反应的早期调节,影响了DLB进展.
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