Dysregulated expression levels of APH1B in peripheral blood are associated with brain atrophy and amyloid-[beta] deposition in Alzheimer's disease

Background The interaction between the brain and periphery might play a crucial role in the development of Alzheimer's disease (AD). Methods Using blood transcriptomic profile data from two independent AD cohorts, we performed expression quantitative trait locus (cis-eQTL) analysis of 29 signif...

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Bibliographic Details
Published in:Alzheimer's research & therapy 2021-11, Vol.13 (1)
Main Authors: Park, Young Ho, Pyun, Jung-Min, Hodges, Angela, Jang, Jae-Won, Bice, Paula J, Kim, SangYun, Saykin, Andrew J, Nho, Kwangsik
Format: Article
Language:English
Subjects:
Alzheimer's disease
Amyloid beta-protein
Atrophy
Brain research
Development and progression
Gene expression
Genetic aspects
Health aspects
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Summary:Background The interaction between the brain and periphery might play a crucial role in the development of Alzheimer's disease (AD). Methods Using blood transcriptomic profile data from two independent AD cohorts, we performed expression quantitative trait locus (cis-eQTL) analysis of 29 significant genetic loci from a recent large-scale genome-wide association study to investigate the effects of the AD genetic variants on gene expression levels and identify their potential target genes. We then performed differential gene expression analysis of identified AD target genes and linear regression analysis to evaluate the association of differentially expressed genes with neuroimaging biomarkers. Results A cis-eQTL analysis identified and replicated significant associations in seven genes (APH1B, BIN1, FCER1G, GATS, MS4A6A, RABEP1, TRIM4). APH1B expression levels in the blood increased in AD and were associated with entorhinal cortical thickness and global cortical amyloid-[beta] deposition. Conclusion An integrative analysis of genetics, blood-based transcriptomic profiles, and imaging biomarkers suggests that APH1B expression levels in the blood might play a role in the pathogenesis of AD. Keywords: Alzheimer's disease, Transcriptome, Blood, Expression quantitative trait locus, Genome-wide association study, Expression, Imaging
ISSN:1758-9193
1758-9193
DOI:10.1186/s13195-021-00919-z