Genome-wide transcriptome analysis of Aβ deposition on PET in a Korean cohort

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.