Alzheimer's disease (AD) is a multifactorial and progressive neurodegenerative disorder characterized by complex interactions among amyloid-β (Aβ) deposition, tau protein hyperphosphorylation, neuroinflammation, oxidative stress, metal dyshomeostasis, and impaired autophagy. Increasing evidence positions neuroinflammation not merely as a secondary response but as a central driver of disease progression, dynamically interacting with amyloid and tau protein pathology and contributing to synaptic dysfunction and neuronal loss. Among inflammatory mechanisms, microglial activation pathways-particularly TREM2 signaling, NLRP3 inflammasome activation, and complement cascade dysregulation-are currently the most clinically actionable targets, supported by genetic, biomarker, and therapeutic evidence. Emerging data suggest that modulation of innate immune pathways is most likely to confer benefit during the prodromal and early symptomatic stages of AD, when neuroinflammatory responses remain partially adaptive and neuronal networks retain functional reserve. Despite decades of drug development, many candidates have failed due to limited efficacy or safety concerns. Recent FDA approvals of anti-amyloid monoclonal antibodies, including aducanumab and lecanemab, represent important advances toward disease-modifying therapy, although their long-term clinical impact and safety profiles remain under evaluation. These developments underscore the importance of biomarker-guided patient selection, disease-stage stratification, and vigilant safety monitoring, particularly regarding amyloid-related imaging abnormalities. Therapeutic strategies are increasingly shifting toward multi-target approaches that integrate amyloid modulation, tau protein-directed interventions, and attenuation of maladaptive neuroinflammatory responses. Concurrently, inflammatory mediators and peripheral metabolic biomarkers are gaining recognition as tools for early detection, risk stratification, and therapeutic response monitoring, potentially enabling precision-based intervention. This review synthesizes current understanding of AD pathogenesis through an inflammation-centered framework, highlighting clinically actionable immune pathways and stage-specific therapeutic windows. By integrating mechanistic insights with biomarker-driven strategies, we aim to delineate translational paths toward more precise, safe, and clinically meaningful disease modification.
