遗传学通过调节生命晚期大脑结构形态的机制影响阿尔茨海默病风险
Roxanna Korologou-Linden1,2, Bing Xu3,4, Elizabeth Coulthard5,6
1Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK rk17685@bristol.ac.uk.
Journal of neurology, neurosurgery, and psychiatry
|April 25, 2024
概括
对阿尔茨海默病 (AD) 的遗传责任影响中年人的大脑结构,而不是早期发育. 这表明AD风险与晚年大脑变化有关,而不是早期的结构性大脑储备.
科学领域:
- 神经遗传学 神经遗传学
- 脑部成像 脑部成像
- 阿尔茨海默氏症疾病研究研究
背景情况:
- 阿尔茨海默病 (AD) 中的神经病理变化可以在几十年之前出现临床症状.
- 研究神经发育和神经退行对AD风险的影响至关重要.
- 了解结构性大脑储备和大脑缩如何影响AD病原是关键.
研究的目的:
- 为了确定对阿尔茨海默病 (AD) 的遗传倾向是否会影响大脑形态.
- 研究神经发育和神经退行在阿尔茨海默病 (AD) 风险中的作用.
- 为了检查大脑结构和阿尔茨海默病 (AD) 风险在整个寿命之间的关系.
主要方法:
- 在五个大队伍中利用双向的双样本孟德尔随机化.
- 在37,680名参与者中,分析了对AD的遗传责任与大脑成像测量 (皮层厚度,内体积,皮层下体积,白质量) 相比.
- 研究了大脑形态对AD风险的影响,使用来自ENIGMA联盟的数据.
主要成果:
- 阿尔茨海默病 (AD) 风险基因基因对中年开始的大脑结构产生年龄相关的影响.
- 在童年和年轻成年期观察到这种影响的证据很弱.
- 在像条形体 (脑膜) 这样的结构中观察到的效应从童年持续到成年后期,只有有限的证据表明大脑形态改变了AD风险.
结论:
- 对阿尔茨海默病 (AD) 的遗传倾向似乎主要通过影响晚年大脑形态的机制影响AD风险.
- 研究结果表明,阿尔茨海默病风险主要不是由发育过程中建立的结构性大脑储备的改变驱动的.
- 需要进行进一步的纵向研究,重复测量以充分阐明潜在机制.
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