DIFFERENTIAL EXPRESSION OF INFLAMMASOME-RELATED GENES IN THE ALZHEIMER’S DISEASE HIPPOCAMPUS: A BIOINFORMATICS PERSPECTIVE

Inflammasomes, multiprotein complexes that modulate inflammatory responses, have emerged as critical players in neurodegeneration, particularly Alzheimer’s disease (AD). Among them, the NOD-like receptor family, pyrin domain-containing 3 (NLRP3), has been most extensively studied, with dysregulated activation linked to amyloid pathology, tau hyperphosphorylation, and neuroinflammation.
This study investigated differentially expressed inflammasome-associated genes (DEGs) in the human hippocampus of AD patients using publicly available transcriptomic datasets. Four RNA-Seq and microarray studies from the GEO database were analysed for DEGs in hippocampal tissues from AD versus control cases. KEGG and Reactome pathway enrichment, as well as protein–protein interaction (PPI) network analyses, were performed to uncover key regulatory nodes involved in the regulation and function of the inflammasome. Core inflammasome genes (NLRP3, NLRP1, AIM2, CASP1, IL1B, IL18, PYCARD, P2RX7, and TXNIP) exhibited inconsistent expression patterns across datasets in AD. However, network analyses revealed the central involvement of TNF/NF-κB signalling, apoptosis, NOD-like receptor signalling, and TRP channels in regulating the inflammasome. Hub and bottleneck genes such as MAPKs, ITPRs, and PLCB4 emerged as critical mediators linking inflammasome activity to hippocampal dysfunction in AD. Although bulk hippocampal transcriptomics revealed limited consistency in direct inflammasome gene dysregulation, integrative network analyses highlighted pathways that converge on inflammasome activation. These results suggest that targeting upstream regulators of inflammasome signalling may hold therapeutic potential in AD.