阿尔茨海默病患者脑白质微观结构异常的系统建模。
Systems modeling of white matter microstructural abnormalities in Alzheimer's disease.
机构信息
Department of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, NY, USA.
Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA.
出版信息
Neuroimage Clin. 2020;26:102203. doi: 10.1016/j.nicl.2020.102203. Epub 2020 Feb 4.
INTRODUCTION
Microstructural abnormalities in white matter (WM) are often reported in Alzheimer's disease (AD). However, it is unclear which brain regions have the strongest WM changes in presymptomatic AD and what biological processes underlie WM abnormality during disease progression.
METHODS
We developed a systems biology framework to integrate matched diffusion tensor imaging (DTI), genetic and transcriptomic data to investigate regional vulnerability to AD and identify genetic risk factors and gene subnetworks underlying WM abnormality in AD.
RESULTS
We quantified regional WM abnormality and identified most vulnerable brain regions. A SNP rs2203712 in CELF1 was most significantly associated with several DTI-derived features in the hippocampus, the top ranked brain region. An immune response gene subnetwork in the blood was most correlated with DTI features across all the brain regions.
DISCUSSION
Incorporation of image analysis with gene network analysis enhances our understanding of disease progression and facilitates identification of novel therapeutic strategies for AD.
简介
在阿尔茨海默病（AD）中，常报道脑白质（WM）的微观结构异常。然而，在 AD 的无症状期，哪些脑区 WM 变化最强，以及在疾病进展过程中，哪些生物学过程导致 WM 异常尚不清楚。
方法
我们开发了一个系统生物学框架，将匹配的弥散张量成像（DTI）、遗传和转录组数据整合在一起，以研究 AD 的区域性易损性，并确定 AD 中 WM 异常的遗传风险因素和基因子网。
结果
我们量化了区域性 WM 异常，并确定了最脆弱的脑区。CELF1 中的 SNP rs2203712 与海马体中几个 DTI 衍生特征最显著相关，海马体是排名最高的脑区。血液中的免疫反应基因子网与所有脑区的 DTI 特征相关性最高。
讨论
将图像分析与基因网络分析相结合，增强了我们对疾病进展的理解，并为 AD 的新型治疗策略提供了便利。
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