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Although mitochondrial dysfunction, redox imbalance, and NLRP3 inflammasome activation have each been implicated in AD pathogenesis, their mechanistic continuity within microglial immunometabolic reprogramming remains insufficiently defined. This narrative review integrates mechanistic, preclinical, and human-relevant evidence to propose a stage-dependent mitochondrial dysfunction\u2013redox imbalance\u2013NLRP3 inflammasome axis. We discuss how AD-related stimuli shift microglia toward a pro-inflammatory metabolic phenotype; how impaired mitochondrial quality control promotes reactive oxygen species generation and oxidized mitochondrial DNA release; and how these signals facilitate NLRP3 inflammasome activation and sustained inflammatory amplification. We further summarize therapeutic strategies targeting upstream mitochondrial homeostasis, intermediate metabolic\u2013redox coupling, and downstream NLRP3 signaling, while emphasizing the translational limitations and biomarker needs. We conclude that this proposed axis provides a testable stage-dependent framework for interpreting chronic, self-amplifying neuroinflammation in AD and may inform biomarker-guided, combinatorial therapeutic strategies.<\/jats:p>","DOI":"10.1177\/13872877261469862","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T14:25:02Z","timestamp":1785507902000},"page":"489-500","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Microglial immunometabolic reprogramming in Alzheimer's disease: From mitochondrial dysfunction and redox imbalance to NLRP3 inflammasome-driven neuroinflammation"],"prefix":"10.1177","volume":"113","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3928-7983","authenticated-orcid":false,"given":"Siyu","family":"Li","sequence":"first","affiliation":[{"name":"Gansu University of Chinese 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