在没有认知障碍的个体中皮层厚度亚型:对皮层稀释的差异网络和转录基因脆弱性
Luigi Lorenzini1,2, Mario Tranfa1,3, Leonard Pieperhoff1,4
1Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centre, Vrije Universiteit, Amsterdam, The Netherlands.
Alzheimer's & dementia : the journal of the Alzheimer's Association
|October 14, 2025
概括
在临床前阶段发现的阿尔茨海默氏病 (AD) 的两种灰质子类型,边缘主导和海马节省,显示出不同的临床特征和进展. 这些亚型为AD病理生理学提供了洞察力.
科学领域:
- 神经成像是一种神经成像.
- 神经病理学神经病理学
- 生物统计学 生物统计学
背景情况:
- 阿尔茨海默氏症 (AD) 灰质的不同亚型,它们的稳定性和导致因素尚未得到充分理解.
- 目前对阿尔茨海默氏病原学的理解缺乏早期灰色质变异的详细表征.
研究的目的:
- 识别和表征在患阿尔茨海默病风险较高的人群中稳定的灰色物质亚型.
- 研究这些亚型之间的临床,人口和纵向进展差异.
- 探索与每个子类型相关的底层网络和转录机制.
主要方法:
- 分析了来自1323名非痴呆症患者的T1w-MRI和粉样蛋白-PET数据,其中622名具有纵向数据.
- 使用非负矩阵因子化 (NMF) 集群识别皮层厚度亚型.
- 通过脑网络模型和成像-转录组学,检查临床/人口差异,亚型稳定性和纵向稀释,并进行复制.
主要成果:
- 确定了两个稳定的灰色物质亚型:边缘主导和海马节约.
- 边缘主导亚型与年龄较大,粉样蛋白负担较高,记忆力下降较快有关.
- 河马节约子类型与注意力和执行功能的更大下降有关,与与网络特性和基因表达相关的明显稀释模式有关.
结论:
- 在临床前的AD中,基于MRI的灰色物质亚型反映了不同的病理生理机制.
- 这些亚型随着时间的推移表现出稳定的特征,有助于预后.
- 特定亚型的纵向皮层稀释遵循不同的网络和转录组机制,为临床试验分层提供信息.
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