Systems modeling of white matter microstructural abnormalities in Alzheimer's disease
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. Method...
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doaj-19614da17c594868af86df231837ea8a2020-11-25T02:09:52ZengElsevierNeuroImage: Clinical2213-15822020-01-0126Systems modeling of white matter microstructural abnormalities in Alzheimer's diseaseEmrin Horgusluoglu-Moloch0Gaoyu Xiao1Minghui Wang2Qian Wang3Xianxiao Zhou4Kwangsik Nho5Andrew J. Saykin6Eric Schadt7Bin Zhang8Department of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, NY, USADepartment of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, NY, USADepartment of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, NY, USADepartment of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, NY, USADepartment of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, NY, USACenter 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, USACenter 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, USADepartment of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, NY, USADepartment of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, NY, USA; Corresponding author at: Department of Genetics & Genomic Sciences, Director, Mount Sinai Center for Transformative Disease Modeling, Member, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029Introduction: 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.http://www.sciencedirect.com/science/article/pii/S2213158220300401Alzheimer's diseaseDiffusion tensor imagingWhite matterBrain regionsCELF1Immune response |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Emrin Horgusluoglu-Moloch Gaoyu Xiao Minghui Wang Qian Wang Xianxiao Zhou Kwangsik Nho Andrew J. Saykin Eric Schadt Bin Zhang |
spellingShingle |
Emrin Horgusluoglu-Moloch Gaoyu Xiao Minghui Wang Qian Wang Xianxiao Zhou Kwangsik Nho Andrew J. Saykin Eric Schadt Bin Zhang Systems modeling of white matter microstructural abnormalities in Alzheimer's disease NeuroImage: Clinical Alzheimer's disease Diffusion tensor imaging White matter Brain regions CELF1 Immune response |
author_facet |
Emrin Horgusluoglu-Moloch Gaoyu Xiao Minghui Wang Qian Wang Xianxiao Zhou Kwangsik Nho Andrew J. Saykin Eric Schadt Bin Zhang |
author_sort |
Emrin Horgusluoglu-Moloch |
title |
Systems modeling of white matter microstructural abnormalities in Alzheimer's disease |
title_short |
Systems modeling of white matter microstructural abnormalities in Alzheimer's disease |
title_full |
Systems modeling of white matter microstructural abnormalities in Alzheimer's disease |
title_fullStr |
Systems modeling of white matter microstructural abnormalities in Alzheimer's disease |
title_full_unstemmed |
Systems modeling of white matter microstructural abnormalities in Alzheimer's disease |
title_sort |
systems modeling of white matter microstructural abnormalities in alzheimer's disease |
publisher |
Elsevier |
series |
NeuroImage: Clinical |
issn |
2213-1582 |
publishDate |
2020-01-01 |
description |
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. |
topic |
Alzheimer's disease Diffusion tensor imaging White matter Brain regions CELF1 Immune response |
url |
http://www.sciencedirect.com/science/article/pii/S2213158220300401 |
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