Neuroinflammation in Alzheimer’s disease: pathogenic signaling, biomarkers, and emerging therapeutic interventions

Alzheimer’s disease (AD) is the leading cause of dementia worldwide, characterized by progressive cognitive decline and neurodegeneration. Although amyloid-β plaques and hyperphosphorylated tau are major pathological hallmarks, increasing evidence highlights persistent neuroinflammation as a critical contributor to disease progression. Activated microglia and astrocytes, inflammatory cytokines, inflammasome activation, and dysregulated immune responses promote neuronal damage and synaptic dysfunction. Similar inflammatory mechanisms are observed in neurological disorders such as multiple sclerosis (MS) and brain tumors, suggesting shared molecular pathways linking neuroinflammation, neurodegeneration, and tumor-associated immune responses. Proteomics, transcriptomics, and multi-omics approaches provide powerful strategies to characterize disease-associated molecular signatures, signaling pathways, biomarkers, and therapeutic targets. This review summarizes key neuroinflammatory mechanisms in AD, including NF-κB, NLRP3, PI3K/Akt, MAPK, cGAS–STING, mitochondrial, lysosomal, calcium, insulin, and blood–brain barrier pathways. Recent advances in proteomic and transcriptomic profiling and their integration with genomic, epigenomic, and metabolomic data are discussed for understanding disease heterogeneity and identifying clinically relevant biomarkers. Current and emerging therapeutic strategies, including anti-Aβ antibodies, anti-inflammatory agents, selective inhibitors, dual-target compounds, PROTACs, and protein–protein interaction modulators, are also evaluated. Finally, multi-omics-based precision medicine and artificial intelligence-assisted analysis may facilitate biomarker-guided patient stratification and development of effective disease-modifying therapies.