Visualizing modules of coordinated structural brain atrophy during the course of conversion to Alzheimer's disease by applying methodology from gene co-expression analysis
Objective: We aimed to identify modularized structural atrophy of brain regions with a high degree of connectivity and its longitudinal changes associated with the progression of Alzheimer's disease (AD) using weighted gene co-expression network analysis (WGCNA), which is an unsupervised hierar...
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Format: | Article |
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Elsevier
2019-01-01
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Series: | NeuroImage: Clinical |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2213158219303079 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kenichiro Sato Tatsuo Mano Hiroshi Matsuda Michio Senda Ryoko Ihara Kazushi Suzuki Hiroyuki Arai Kenji Ishii Kengo Ito Takeshi Ikeuchi Ryozo Kuwano Tatsushi Toda Takeshi Iwatsubo Atsushi Iwata |
spellingShingle |
Kenichiro Sato Tatsuo Mano Hiroshi Matsuda Michio Senda Ryoko Ihara Kazushi Suzuki Hiroyuki Arai Kenji Ishii Kengo Ito Takeshi Ikeuchi Ryozo Kuwano Tatsushi Toda Takeshi Iwatsubo Atsushi Iwata Visualizing modules of coordinated structural brain atrophy during the course of conversion to Alzheimer's disease by applying methodology from gene co-expression analysis NeuroImage: Clinical |
author_facet |
Kenichiro Sato Tatsuo Mano Hiroshi Matsuda Michio Senda Ryoko Ihara Kazushi Suzuki Hiroyuki Arai Kenji Ishii Kengo Ito Takeshi Ikeuchi Ryozo Kuwano Tatsushi Toda Takeshi Iwatsubo Atsushi Iwata |
author_sort |
Kenichiro Sato |
title |
Visualizing modules of coordinated structural brain atrophy during the course of conversion to Alzheimer's disease by applying methodology from gene co-expression analysis |
title_short |
Visualizing modules of coordinated structural brain atrophy during the course of conversion to Alzheimer's disease by applying methodology from gene co-expression analysis |
title_full |
Visualizing modules of coordinated structural brain atrophy during the course of conversion to Alzheimer's disease by applying methodology from gene co-expression analysis |
title_fullStr |
Visualizing modules of coordinated structural brain atrophy during the course of conversion to Alzheimer's disease by applying methodology from gene co-expression analysis |
title_full_unstemmed |
Visualizing modules of coordinated structural brain atrophy during the course of conversion to Alzheimer's disease by applying methodology from gene co-expression analysis |
title_sort |
visualizing modules of coordinated structural brain atrophy during the course of conversion to alzheimer's disease by applying methodology from gene co-expression analysis |
publisher |
Elsevier |
series |
NeuroImage: Clinical |
issn |
2213-1582 |
publishDate |
2019-01-01 |
description |
Objective: We aimed to identify modularized structural atrophy of brain regions with a high degree of connectivity and its longitudinal changes associated with the progression of Alzheimer's disease (AD) using weighted gene co-expression network analysis (WGCNA), which is an unsupervised hierarchical clustering method originally used in genetic analysis. Methods: We included participants with late mild cognitive impairment (MCI) at baseline from the Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) study. We imputed normalized and Z-transformed structural volume or cortical thickness data of 164 parcellated brain regions/structures based on the calculations of the FreeSurfer software. We applied the WGCNA to extract modules with highly interconnected structural atrophic patterns and examined the correlation between the identified modules and clinical AD progression. Results: We included 204 participants from the baseline dataset, and performed a follow-up with 100 in the 36-month dataset of MCI cohort participants from the J-ADNI. In the univariate correlation or variable importance analysis, baseline atrophy in temporal lobe regions/structures significantly predicted clinical AD progression. In the WGCNA consensus analysis, co-atrophy modules associated with MCI conversion were first distributed in the temporal lobe and subsequently extended to adjacent parietal cortical regions in the following 36 months. Conclusions: We identified coordinated modules of brain atrophy and demonstrated their longitudinal extension along with the clinical course of AD progression using WGCNA, which showed a good correspondence with previous pathological studies of the tau propagation theory. Our results suggest the potential applicability of this methodology, originating from genetic analyses, for the surrogate visualization of the underlying pathological progression in neurodegenerative diseases not limited to AD. Keywords: Brain atrophy, Mild cognitive impairment, Alzheimer's disease module, Hierarchical clustering, Connectivity |
url |
http://www.sciencedirect.com/science/article/pii/S2213158219303079 |
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doaj-a9722dae035042dab31cc5612ca6c6682020-11-25T01:52:35ZengElsevierNeuroImage: Clinical2213-15822019-01-0124Visualizing modules of coordinated structural brain atrophy during the course of conversion to Alzheimer's disease by applying methodology from gene co-expression analysisKenichiro Sato0Tatsuo Mano1Hiroshi Matsuda2Michio Senda3Ryoko Ihara4Kazushi Suzuki5Hiroyuki Arai6Kenji Ishii7Kengo Ito8Takeshi Ikeuchi9Ryozo Kuwano10Tatsushi Toda11Takeshi Iwatsubo12Atsushi Iwata13Department of Neurology, Graduate School of Medicine, University of Tokyo, Japan; Corresponding authors at: Department of Neurology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-8655, Japan.Department of Neurology, Graduate School of Medicine, University of Tokyo, JapanNational Center for Neurology and Psychiatry, Kodaira, JapanKobe City Medical Center General Hospital, Kobe, JapanDepartment of Neurology, Graduate School of Medicine, University of Tokyo, Japan; Unit for Early and Exploratory Clinical Development, The University of Tokyo Hospital, Tokyo, JapanDepartment of Neurology, Graduate School of Medicine, University of Tokyo, Japan; Unit for Early and Exploratory Clinical Development, The University of Tokyo Hospital, Tokyo, JapanDepartment of Geriatrics & Gerontology, Division of Brain Science, Institute of Development, Aging and Cancer (IDAC), Tohoku University, JapanTokyo Metropolitan Institute of Gerontology, Tokyo, JapanNational Center for Geriatrics and Gerontology, Obu, JapanNiigata University, Niigata, JapanNiigata University, Niigata, JapanDepartment of Neurology, Graduate School of Medicine, University of Tokyo, JapanUnit for Early and Exploratory Clinical Development, The University of Tokyo Hospital, Tokyo, Japan; Department of Neuropathology, Graduate School of Medicine, University of Tokyo, JapanDepartment of Neurology, Graduate School of Medicine, University of Tokyo, Japan; Corresponding authors at: Department of Neurology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-8655, Japan.Objective: We aimed to identify modularized structural atrophy of brain regions with a high degree of connectivity and its longitudinal changes associated with the progression of Alzheimer's disease (AD) using weighted gene co-expression network analysis (WGCNA), which is an unsupervised hierarchical clustering method originally used in genetic analysis. Methods: We included participants with late mild cognitive impairment (MCI) at baseline from the Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) study. We imputed normalized and Z-transformed structural volume or cortical thickness data of 164 parcellated brain regions/structures based on the calculations of the FreeSurfer software. We applied the WGCNA to extract modules with highly interconnected structural atrophic patterns and examined the correlation between the identified modules and clinical AD progression. Results: We included 204 participants from the baseline dataset, and performed a follow-up with 100 in the 36-month dataset of MCI cohort participants from the J-ADNI. In the univariate correlation or variable importance analysis, baseline atrophy in temporal lobe regions/structures significantly predicted clinical AD progression. In the WGCNA consensus analysis, co-atrophy modules associated with MCI conversion were first distributed in the temporal lobe and subsequently extended to adjacent parietal cortical regions in the following 36 months. Conclusions: We identified coordinated modules of brain atrophy and demonstrated their longitudinal extension along with the clinical course of AD progression using WGCNA, which showed a good correspondence with previous pathological studies of the tau propagation theory. Our results suggest the potential applicability of this methodology, originating from genetic analyses, for the surrogate visualization of the underlying pathological progression in neurodegenerative diseases not limited to AD. Keywords: Brain atrophy, Mild cognitive impairment, Alzheimer's disease module, Hierarchical clustering, Connectivityhttp://www.sciencedirect.com/science/article/pii/S2213158219303079 |