The Role of Neuroinflammation in Alzheimer's Disease: Molecular Mechanisms and Emerging Therapeutic Approaches

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder traditionally characterized by amyloid-beta (Aβ) accumulation, tau pathology, synaptic dysfunction, and neuronal loss. Increasing evidence indicates that neuroinflammation is not merely a secondary consequence of neurodegeneration but an important component of AD pathogenesis. This review examines the molecular and cellular mechanisms through which neuroinflammation contributes to the progression of AD, with particular emphasis on microglial activation, TREM2 and soluble TREM2 (sTREM2) signaling, NLRP3 inflammasome activation, astrocyte–microglia interactions, and blood–brain barrier dysfunction. The review further evaluates emerging therapeutic strategies aimed at modulating these pathways, including NLRP3 inhibition, TREM2/sTREM2-targeted approaches, restoration of glial homeostasis, cytokine modulation, and pro-resolving strategies. Current evidence suggests that inflammatory responses may exert both protective and detrimental effects depending on disease stage, duration, and cellular context. Consequently, broad suppression of neuroinflammation may be insufficient and potentially counterproductive. Future therapeutic development may benefit from precision immunomodulation guided by disease-stage-specific biomarkers and molecular profiling. Understanding the complex interactions between neuroinflammation, pathological protein accumulation, glial dysfunction, and neurovascular abnormalities may therefore provide new opportunities for developing disease-modifying approaches to Alzheimer’s disease.