Dysregulated expression levels of APH1B in peripheral blood are associated with brain atrophy and amyloid-β 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 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-β 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13195-021-00919-z.