Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Department of Diagnostic Radiology and Nuclear Medicine, Rush University Medical Center, Chicago, IL, USA.
Brain Imaging Behav. 2019 Aug;13(4):963-972. doi: 10.1007/s11682-018-9910-4.
Cognitive function relies on both molecular levels and cellular structures. However, systematic relationships between these two components of cognitive function, and their joint contribution to disease, are largely unknown. We utilize postmortem neuroimaging in tandem with gene expression and DNA methylation, from 222 deeply-phenotyped persons in a longitudinal aging cohort. Expression of hundreds of genes and methylation at thousands of loci are related to the microstructure of extensive regions of this same set of brains, as assessed by MRI. The genes linked to brain microstructure perform functions related to cell motility, transcriptional regulation and nuclear processes, and are selectively associated with Alzheimer's phenotypes. Similar methodology can be applied to other diseases to identify their joint molecular and structural basis, or to infer molecular levels in the brain on the basis of neuroimaging for precision medicine applications.
认知功能依赖于分子水平和细胞结构。然而，认知功能的这两个组成部分之间的系统关系，以及它们对疾病的共同贡献，在很大程度上是未知的。我们利用 222 名在纵向老化队列中深度表型的人的死后神经影像学，以及基因表达和 DNA 甲基化数据。数百个基因的表达和数千个位点的甲基化与同一组大脑的广泛区域的微观结构有关，通过 MRI 评估。与大脑微观结构相关的基因发挥与细胞运动、转录调控和核过程相关的功能，并且与阿尔茨海默病表型选择性相关。类似的方法可以应用于其他疾病，以确定它们的共同分子和结构基础，或基于神经影像学为精准医疗应用推断大脑中的分子水平。
