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Alzheimers. Dement., Feb 2025, 21 (2) | https://doi.org/10.1002/alz.14563
Transcriptome analysis of early- and late-onset Alzheimer's disease in Korean cohorts
Sang-Won Han1,2, Jiyun Hwang3, Tamina Park4, Jung-Min Pyun1, Joo-Yeon Lee3,5, Jeong Su Park6, Paula J. Bice4, Shiwei Liu4, Sunmin Yun7, Jibin Jeong7, Shannon L. Risacher4, Andrew J. Saykin4, Min Soo Byun8, Dahyun Yi9, Joohon Sung3,5, Dong Young Lee8, SangYun Kim10, Kwangsik Nho4, Young Ho Park10
1 Department of Neurology, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea
2 Department of Neurology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon-si, Republic of Korea
3 Genome and Health Big Data Laboratory, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea
4 Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana Alzheimer’s Disease Research Center, Indiana University School of Medicine, Indianapolis, Indiana, USA
5 Institute of Health and Environments, Seoul National University, Seoul, Republic of Korea
6 Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Republic of Korea
7 Precision Medicine Center, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea
8 Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea
9 Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Seoul, Republic of Korea
10 Department of Neurology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, Seongnam-si, Republic of Korea
Sang-Won Han, Jiyun Hwang, Tamina Park, and Jung-Min Pyun contributed equally to this work.
Correspondence: Kwangsik Nho, Young Ho Park
1 Department of Neurology, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea
2 Department of Neurology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon-si, Republic of Korea
3 Genome and Health Big Data Laboratory, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea
4 Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana Alzheimer’s Disease Research Center, Indiana University School of Medicine, Indianapolis, Indiana, USA
5 Institute of Health and Environments, Seoul National University, Seoul, Republic of Korea
6 Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Republic of Korea
7 Precision Medicine Center, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea
8 Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea
9 Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Seoul, Republic of Korea
10 Department of Neurology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, Seongnam-si, Republic of Korea
Sang-Won Han, Jiyun Hwang, Tamina Park, and Jung-Min Pyun contributed equally to this work.
Correspondence: Kwangsik Nho, Young Ho Park
Abstract
Introduction: The molecular mechanisms underlying early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) remain incompletely understood, particularly in Asian populations.
Methods: RNA-sequencing was carried out on blood samples from 248 participants in the Seoul National University Bundang Hospital cohort to perform differential gene expression (DGE) and weighted gene co-expression network analysis. Findings were replicated in an independent Korean cohort (N = 275).
Results: DGE analysis identified 18 and 88 dysregulated genes in EOAD and LOAD, respectively. Network analysis identified a LOAD-associated module showing a significant enrichment in pathways related to mitophagy, 5' adenosine monophosphate-activated protein kinase signaling, and ubiquitin-mediated proteolysis. In the replication cohort, downregulation of SMOX and PLVAP in LOAD was replicated, and the LOAD-associated module was highly preserved. In addition, SMOX and PLVAP were associated with brain amyloid beta deposition.
Discussion: Our findings suggest distinct molecular signatures for EOAD and LOAD in a Korean population, providing deeper understanding of their diagnostic potential and molecular mechanisms.
Highlights: Analysis identified 18 and 88 dysregulated genes in early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD), respectively. Expression levels of SMOX and PLVAP were downregulated in LOAD. Expression levels of SMOX and PLVAP were associated with brain amyloid beta deposition. Pathways including mitophagy and 5' adenosine monophosphate-activated protein kinase signaling were enriched in a LOAD module. A LOAD module was highly preserved across two independent cohorts.
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Methods: RNA-sequencing was carried out on blood samples from 248 participants in the Seoul National University Bundang Hospital cohort to perform differential gene expression (DGE) and weighted gene co-expression network analysis. Findings were replicated in an independent Korean cohort (N = 275).
Results: DGE analysis identified 18 and 88 dysregulated genes in EOAD and LOAD, respectively. Network analysis identified a LOAD-associated module showing a significant enrichment in pathways related to mitophagy, 5' adenosine monophosphate-activated protein kinase signaling, and ubiquitin-mediated proteolysis. In the replication cohort, downregulation of SMOX and PLVAP in LOAD was replicated, and the LOAD-associated module was highly preserved. In addition, SMOX and PLVAP were associated with brain amyloid beta deposition.
Discussion: Our findings suggest distinct molecular signatures for EOAD and LOAD in a Korean population, providing deeper understanding of their diagnostic potential and molecular mechanisms.
Highlights: Analysis identified 18 and 88 dysregulated genes in early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD), respectively. Expression levels of SMOX and PLVAP were downregulated in LOAD. Expression levels of SMOX and PLVAP were associated with brain amyloid beta deposition. Pathways including mitophagy and 5' adenosine monophosphate-activated protein kinase signaling were enriched in a LOAD module. A LOAD module was highly preserved across two independent cohorts.
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논문정보
- Research article
- 2025년 02월 (BRIC 등록일 2025-02-13)
- 국내(교신)+국외 연구진
- 의약학 > 신경의학
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