枢纽中断的增加与自体主导性阿尔茨海默氏症中痴呆症严重程度的并行
Jiaxin Cindy Tu1, Peter R Millar2, Jeremy F Strain2
1Department of Radiology, Washington University in St. Louis, St. Louis, MO, USA, 63108.
bioRxiv : the preprint server for biology
|November 14, 2023
概括
阿尔茨海默氏症 (AD) 中的大脑枢纽的干扰遵循一个有针对性的攻击模式,在症状出现前几年就能检测到. 这种脆弱性与高的神经元活动有关,这表明活动依赖性退化是AD进展的关键机制.
科学领域:
- 神经科学是一个神经科学.
- 神经退行性疾病 神经退行性疾病
- 大脑网络分析 脑网络分析
背景情况:
- 大脑枢纽对于信息传输至关重要,但在像阿尔茨海默病 (AD) 这样的神经退行性疾病中是脆弱的.
- 在AD中观察到枢纽干扰,计算模型表明由于高神经元活动导致"活动依赖性退化".
- 之前的研究缺乏针对性中心攻击与随机损伤以及AD活动依赖机制的确切人类证据.
研究的目的:
- 为了确定AD中的枢纽区域是否受到有针对性的攻击或随机损害,使用精制的枢纽中断指数.
- 通过将枢纽脆弱性与全球连接和功能系统变异联系起来,调查AD活动依赖性退化证据.
- 在临床前ADAD中确定与粉样β (Aβ) 沉积和症状发作有关的枢纽干扰的时间表.
主要方法:
- 应用了精细的枢纽干扰指数来分析自体主导性阿尔茨海默病 (ADAD) 参与者的大脑网络变化.
- 根据全球连接和功能系统之间的连接差异评估了枢纽漏洞.
- 通过PET成像和预期的症状出现,评估了与粉样β (Aβ) 沉积相对的枢纽干扰的时间.
主要成果:
- 在ADAD中确定了枢纽干扰的有针对性的攻击模式,即使在临床前阶段也很明显.
- 枢纽干扰的严重程度与症状进展相关,并且在预期的症状发作之前可检测到8年.
- 枢纽中断主要与全球连接的区域差异有关,并顺序跟随Aβ沉积,支持活动依赖性退化.
结论:
- 研究结果支持在AD中针对大脑枢纽的有针对性的攻击模型,并表明活动依赖性退化是枢纽脆弱性的根本原因.
- 枢纽干扰是阿尔茨海默病的早期和渐进性特征,具有作为临床前生物标志物的潜力.
- 了解枢纽地区的活动依赖性退化,可以为阿尔茨海默病的新型诊断和治疗策略提供信息.
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