迈向阿尔茨海默氏症病的级联遗传风险
Andre Altmann1, Leon M Aksman2, Neil P Oxtoby3
1UCL Centre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering, University College London, London, WC1E 6BT, UK.
阿尔茨海默病 (AD) 的遗传风险在不同阶段不同影响疾病的进展. APOE-e4在早期的粉样蛋白/tau积累中至关重要,而随着神经退行进展,多基因风险变得越来越重要.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 遗传学 是一个
- 生物标志物 生物标志物
背景情况:
- 阿尔茨海默病 (AD) 的进展是分阶段使用粉样蛋白 (A), (T) 和神经退行 (N) 生物标志物 (ATN框架).
- 全基因组关联研究已经确定了与晚期发作的AD相关的众多遗传基因位点.
- 遗传风险对阿尔茨海默氏症进展的阶段性贡献仍然不完全理解.
研究的目的:
- 调查AD的遗传风险因素是否对疾病进展具有阶段依赖的影响.
- 区分APOE和多基因风险评分在ATN生物标志物阶段之间的过渡中的作用.
主要方法:
- 利用了来自阿尔茨海默病神经成像计划 (ADNI) 队列的数据.
- 采用考克斯的比例危险模型来分析具有AT和AT+T状态的参与者的生物标志物转换.
- 评估了APOE和多基因风险评分对过渡到A+T和A+T+阶段的影响,并根据年龄,性别和教育进行调整.
主要成果:
- APOE-e4显著预测了从A-T-转换为A+T- (HR=2.88),而多基因风险没有.
- 对于从A+T-到A+T+的进展,APOE-e4的效果下降 (HR=1.62),多基因风险变得显著 (HR=1.73).
- 在早期的转变中,APOE-e4同位素的效果比异位素的效果更强.
结论:
- 晚期发病的AD的遗传风险以阶段依赖的方式展开.
- 了解疾病阶段和遗传风险之间的相互作用对于阐明AD病变的发病过程至关重要.
- 这种知识可能会揭示干预ATN阶段过渡的治疗目标.
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