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Alzheimers. Dement., 08 November 2024 | https://doi.org/10.1002/alz.14348
Genome-wide transcriptome analysis of Aβ deposition on PET in a Korean cohort
Tamina Park 1,2, Jiyun Hwang 3, Shiwei Liu 1,2, Soumilee Chaudhuri 1,2,4, Sang Won Han 5, Dahyun Yi 6, Min Soo Byun 7,8, Yen-Ning Huang 1,2, Thea Rosewood 1,2, Gijung Jung 7, Min Jeong Kim 7, Hyejin Ahn 7, Jun-Young Lee 9, Yu Kyeong Kim 9, MinYoung Cho 1,2, Paula J Bice 1,2, Hannah Craft 1,2, Shannon L. Risacher 1,2,3, Hongyu Gao 10,11, Yunlong Liu 10,11,12, SangYun Kim 13, Young Ho Park 13, Dong Young Lee 6,7,8, Andrew J Saykin 1,2,3,10, Kwangsik Nho 1,2,14
1Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, USA.
2Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.
3Genome and Health Big Data Laboratory Graduate School of Public Health, , Seoul National University, Seoul, South Korea.
4Medical Neuroscience Graduate Program, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, USA.
5Department of Neurology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon-si, South Korea.
6Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Seoul, South Korea.
7Department of Neuropsychiatry, Seoul National University Hospital, Seoul, South Korea.
8Department of Psychiatry, Seoul National University College of Medicine, Seoul, South Korea.
9Department of Psychiatry, Seoul National University Boramae Medical Center, Seoul, South Korea.
10Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
11Center for Medical Genomics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
12Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
13Department of Neurology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, Seongnam-si, South Korea.
14School of Informatics and Computing, Indiana University, Indianapolis, Indiana, USA.
Corresponding Authors: Dong Young Lee, Andrew J. Saykin, and Kwangsik Nho
1Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, USA.
2Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.
3Genome and Health Big Data Laboratory Graduate School of Public Health, , Seoul National University, Seoul, South Korea.
4Medical Neuroscience Graduate Program, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, USA.
5Department of Neurology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon-si, South Korea.
6Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Seoul, South Korea.
7Department of Neuropsychiatry, Seoul National University Hospital, Seoul, South Korea.
8Department of Psychiatry, Seoul National University College of Medicine, Seoul, South Korea.
9Department of Psychiatry, Seoul National University Boramae Medical Center, Seoul, South Korea.
10Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
11Center for Medical Genomics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
12Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
13Department of Neurology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, Seongnam-si, South Korea.
14School of Informatics and Computing, Indiana University, Indianapolis, Indiana, USA.
Corresponding Authors: Dong Young Lee, Andrew J. Saykin, and Kwangsik Nho
Abstract
Introduction: Despite the recognized importance of including ethnic diversity in Alzheimer's disease (AD) research, substantial knowledge gaps remain, particularly in Asian populations.
Methods: RNA sequencing was performed on blood samples from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) to perform differential gene expression (DGE), gene co-expression network, gene-set enrichment, and machine learning analyses for amyloid beta (Aβ) deposition on positron emission tomography.
Results: DGE analysis identified 265 dysregulated genes associated with Aβ deposition and replicated three AD-associated genes in an independent Korean cohort. Network analysis identified two modules related to pathways including a natural killer (NK) cell-mediated immunity. Machine learning analysis showed the classification of Aβ positivity improved with the inclusion of gene expression data.
Discussion: Our results in a Korean population suggest Aβ deposition-associated genes are enriched in NK cell-mediated immunity, providing a better understanding of AD molecular mechanisms and yielding potential diagnostic and therapeutic strategies.
Highlights: Dysregulated genes were associated with amyloid beta (Aβ) deposition on positron emission tomography in a Korean cohort. Dysregulated genes in Alzheimer's disease were replicated in an independent Korean cohort. Gene network modules were associated with Aβ deposition. Natural killer (NK) cell proportion in blood was associated with Aβ deposition. Dysregulated genes were related to a NK cell-mediated immunity.
Methods: RNA sequencing was performed on blood samples from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) to perform differential gene expression (DGE), gene co-expression network, gene-set enrichment, and machine learning analyses for amyloid beta (Aβ) deposition on positron emission tomography.
Results: DGE analysis identified 265 dysregulated genes associated with Aβ deposition and replicated three AD-associated genes in an independent Korean cohort. Network analysis identified two modules related to pathways including a natural killer (NK) cell-mediated immunity. Machine learning analysis showed the classification of Aβ positivity improved with the inclusion of gene expression data.
Discussion: Our results in a Korean population suggest Aβ deposition-associated genes are enriched in NK cell-mediated immunity, providing a better understanding of AD molecular mechanisms and yielding potential diagnostic and therapeutic strategies.
Highlights: Dysregulated genes were associated with amyloid beta (Aβ) deposition on positron emission tomography in a Korean cohort. Dysregulated genes in Alzheimer's disease were replicated in an independent Korean cohort. Gene network modules were associated with Aβ deposition. Natural killer (NK) cell proportion in blood was associated with Aβ deposition. Dysregulated genes were related to a NK cell-mediated immunity.
논문정보
- Research article
- 2024년 11월 (BRIC 등록일 2024-11-14)
- 국내(교신)+국외 연구진
- 생명과학 > 유전학
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