在老龄化和阿尔茨海默病小鼠模型中,TREM1 破坏了骨髓细胞的生物能量和认知功能
Edward N Wilson1,2, Congcong Wang1, Michelle S Swarovski1
1Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Nature neuroscience
|March 28, 2024
概括
在阿尔茨海默病的小鼠模型中,TREM1 缺陷可以防止与年龄相关的认知衰退和骨髓质功能障碍. 这表明TREM1是神经炎症和记忆丧失的关键驱动因素,提供了潜在的治疗点.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
背景情况:
- 人类遗传学将缺陷的骨髓质反应与晚发性阿尔茨海默病 (AD) 联系起来.
- 衰老会损害骨髓质代谢和免疫功能,导致神经退行.
- 在神经退行性疾病中,TREM1 (在髓状细胞表达的触发受体1),一种促炎因素的作用仍然不清楚.
研究的目的:
- 调查TREM1在年龄相关的骨髓功能障碍和阿尔茨海默病的认知衰退中的作用.
- 为了确定TREM1缺乏是否影响粉样β病理和相关的神经炎症.
主要方法:
- 在5XFAD和APPSwe小鼠模型中利用了Trem1缺乏的小鼠和TREM1平分不足的小鼠.
- 评估了骨髓质代谢,炎症,海马体记忆功能和微质形态.
- 在体外分析了微质对粉样β寡合体的反应.
- 在死后人类阿尔茨海默病大脑中检查了TREM1表达.
主要成果:
- Trem1 缺乏防止了骨髓质代谢 (例如,核糖5-酸盐) 和炎症的年龄相关下降.
- 缺乏Trem1的微质细胞对粉样β寡合体诱导的代谢干扰具有抗性.
- 在小鼠模型中TREM1缺陷挽救了空间记忆丧失,保持了微质平衡,并减少了神经病理.
- 人类AD大脑中的TREM1表达与疾病严重程度相关.
结论:
- 通过驱动骨髓功能障碍和神经炎症,TREM1促进衰老和阿尔茨海默病的认知衰退.
- 准TREM1可能为阿尔茨海默病提供一种新的治疗策略.
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