核心1阿尔茨海默病生物标志物的多基因分数预测了早期的认知和病理变化
Yuexuan Xu1,2, Min Qiao1,2, Tamil I Gunasekaran1,2
1Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Alzheimer's & dementia : the journal of the Alzheimer's Association
|November 27, 2025
概括
早期阿尔茨海默病 (AD) 生物标志物的遗传分数比临床AD遗传分数更好地预测AD病理和认知衰退. 这表明可以改善早期检测和预测AD进展的潜力.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
- 生物标志物 生物标志物
背景情况:
- 阿尔茨海默病 (AD) 的特点是早期的生物变化被核心1生物标志物捕获.
- APOE是已知的遗传风险因素,但其他遗传变异在核心1生物标志物的作用尚未完全理解.
研究的目的:
- 调查核心1生物标志物水平的遗传调节器是否比临床AD的遗传调节器更好地预测AD病理.
- 评估多基因分数 (PGS) 对核心1生物标志物的预测价值与不同人群中的临床AD.
主要方法:
- 全基因组关联研究 (GWAS) 用于在非西班牙裔白人个体中构建amyloid PET,血p-tau181,CSF p-tau181和临床AD的PGS.
- 使用血p-tau181和临床AD GWASs开发了西班牙裔特异性的PGS.
- 与血生物标志物和认知的关联被纵向评估,在单独的队列中进行复制.
主要成果:
- 在非西班牙裔白人和西班牙裔人口中,与AD PGS相比,核心1生物标志物PGS证明了AD病理和相关认知表现的优越预测.
- APOE ε4 解释了血p-tau217 的更多变异,而不是血p-tau181.
结论:
- 基于核心1生物标志物的PGS显示了AD相关的血生物标志物和早期认知变化的增强预测价值.
- 虽然预测性改进是适度的,但不同的遗传信号表明,集成性Core 1 PGS有可能改善血p-tau水平的预测.
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