Transcriptome analysis of early- and late-onset Alzheimer's disease in Korean cohorts

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.