生物标志物 生物标志物
Mario Tranfa1, Leonard Pieperhoff1, Giuseppe Pontillo1,2,3
1Amsterdam University Medical Center (Amsterdam UMC), Amsterdam, North Holland, Netherlands.
Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 25, 2025
概括
阿尔茨海默病 (AD) 的多基因风险得分影响白质 (WM) 完整性. 遗传易感性与AD病理相互作用,通过不同的生物学途径影响WM纤维密度和横截面.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 遗传学是一种遗传学.
- 生物标志物 生物标志物
背景情况:
- 阿尔茨海默病 (AD) 诊断正在转向像粉样蛋白-β1-42 (Aβ1-42) 和酸化-Tau181 (p-Tau181) 这样的生物标志物.
- 并非所有Aβ1-42沉积的个体都会发展为AD,这表明其他因素也会影响疾病的易感性.
- 多基因路径及其与AD病理学的相互作用可能解释大脑易感性的变化.
研究的目的:
- 调查特定途径的多基因风险评分 (PRS) 对白质 (WM) 完整性的影响.
- 探索AD病理 (Aβ1-42,p-Tau181) 和PRS在调节WM纤维密度 (FD) 和纤维截面 (FC) 之间的相互作用.
- 利用基于fixel的方法来分析与遗传风险和AD生物标志物相关的WM变化.
主要方法:
- 来自欧洲预防阿尔茨海默氏症痴呆症 (EPAD) 队列的803名非痴呆症参与者的分析.
- 进行了基因组测序,脑脊液 (CSF) Aβ1-42和p-Tau181测量以及扩散MRI测量.
- 路径特定的PRS是基于由生物功能分组的AD相关遗传变异构建的. 线性模型评估了对FD和FC的影响,并对共变量和多重比较进行了校正.
主要成果:
- p-Tau181表现出与FD的多相关系.
- 迁移途径PRS与增加的FD和FC有关,特别是在左半球.
- Aβ1-42和p-Tau181分别调节了清除和免疫激活途径PRS对FD的影响,证明了病理依赖的遗传影响.
结论:
- 阿尔茨海默病的多基因风险直接影响了WM的完整性.
- 对临床前AD病理学的遗传易感性涉及特定的生物过程,这些过程会对WM完整性产生差异性影响.
- 了解这些相互作用对于阐明AD病原和变异性至关重要.
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