Transcriptome analysis of early- and late-onset Alzheimer's disease in Korean cohorts.
| Title: | Transcriptome analysis of early- and late-onset Alzheimer's disease in Korean cohorts. |
|---|---|
| Authors: | Han SW; Department of Neurology, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea.; Department of Neurology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon-si, Republic of Korea.; Hwang J; Genome and Health Big Data Laboratory, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea.; Park T; Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.; Pyun JM; Department of Neurology, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea.; Lee JY; Genome and Health Big Data Laboratory, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea.; Institute of Health and Environments, Seoul National University, Seoul, Republic of Korea.; Park JS; Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Republic of Korea.; Bice PJ; Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.; Liu S; Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.; Yun S; Precision Medicine Center, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea.; Jeong J; Precision Medicine Center, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea.; Risacher SL; Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.; Saykin AJ; Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.; Byun MS; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.; Yi D; Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Seoul, Republic of Korea.; Sung J; Genome and Health Big Data Laboratory, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea.; Institute of Health and Environments, Seoul National University, Seoul, Republic of Korea.; Lee DY; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.; Kim S; Department of Neurology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, Seongnam-si, Republic of Korea.; Nho K; Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.; Park YH; Department of Neurology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, Seongnam-si, Republic of Korea. |
| Source: | Alzheimer's & dementia : the journal of the Alzheimer's Association [Alzheimers Dement] 2025 Feb; Vol. 21 (2), pp. e14563. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: John Wiley & Sons, Ltd Country of Publication: United States NLM ID: 101231978 Publication Model: Print Cited Medium: Internet ISSN: 1552-5279 (Electronic) Linking ISSN: 15525260 NLM ISO Abbreviation: Alzheimers Dement Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2020- : Hoboken, NJ : John Wiley & Sons, Ltd.; Original Publication: Orlando, FL : Elsevier, Inc. |
| MeSH Terms: | Alzheimer Disease*/genetics ; Gene Expression Profiling* ; Transcriptome*; Republic of Korea/epidemiology ; Amyloid beta-Peptides/metabolism ; Humans ; Male ; Female ; Cohort Studies ; Aged ; Age of Onset ; Middle Aged |
| 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.; (© 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.) |
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| Grant Information: | T32 AG071444 United States AG NIA NIH HHS; U01 AG068057 United States AG NIA NIH HHS; R01 AG19771 United States AG NIA NIH HHS; UL1 TR001108 United States TR NCATS NIH HHS; U19 AG024904 United States AG NIA NIH HHS; P30 AG10133 United States AG NIA NIH HHS; P50GM115318 United States GM NIGMS NIH HHS; R01 AG061788 United States AG NIA NIH HHS; P30 AG072976 United States AG NIA NIH HHS; R03 AG063250 United States AG NIA NIH HHS; R01 LM013463 United States LM NLM NIH HHS; P50 GM115318 United States GM NIGMS NIH HHS; R01 AG019771 United States AG NIA NIH HHS; U01 AG072177 United States AG NIA NIH HHS; P30 AG010133 United States AG NIA NIH HHS; U19 AG074879 United States AG NIA NIH HHS; U01 AG024904 United States AG NIA NIH HHS; K01 AG049050 United States AG NIA NIH HHS; R01 AG057739 United States AG NIA NIH HHS; R01 AG068193 United States AG NIA NIH HHS; R01 LM012535 United States LM NLM NIH HHS |
| Contributed Indexing: | Keywords: Alzheimer's disease; East Asians; differentially expressed genes; early‐onset Alzheimer's disease; late‐onset Alzheimer's disease; weighted gene co‐expression network analysis |
| Substance Nomenclature: | 0 (Amyloid beta-Peptides) |
| Entry Date(s): | Date Created: 20250212 Date Completed: 20250507 Latest Revision: 20260518 |
| Update Code: | 20260519 |
| PubMed Central ID: | PMC11815242 |
| DOI: | 10.1002/alz.14563 |
| PMID: | 39935412 |
| Database: | MEDLINE |
Journal Article