Meta-analysis and transcriptomic analysis reveal that NKRF and ZBTB17 regulate the NF-κB signaling pathway, contributing to the shared molecular mechanisms of Alzheimer's disease and atherosclerosis.

Abstract

Alzheimer's disease (AD) and atherosclerosis (AS) are widespread diseases predominantly observed in the elderly population. Despite their prevalence, the underlying molecular interconnections between these two conditions are not well understood. Utilizing meta-analysis, bioinformatics methodologies, and the GEO database, we systematically analyzed transcriptome data to pinpoint key genes concurrently differentially expressed in AD and AS. Our experimental validations in mouse models highlighted the prominence of two genes, NKRF (NF-κB-repressing factor) and ZBTB17 (MYC-interacting zinc-finger protein 1). These genes appear to influence the progression of both AD and AS by modulating the NF-κB signaling pathway, as confirmed through subsequent invitro and invivo studies. This research uncovers a novel shared molecular pathway between AD and AS, underscoring the significant roles of NKRF and ZBTB17 in the pathogenesis of these disorders.