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This review examines these metabolic changes across disease stages, brain regions, and plaque\u2010associated microenvironments and proposes a dynamic state\u2010composition model. In this model, microglia in different metabolic states coexist, and their relative proportions and spatial distribution change as AD progresses. In early disease or during active phagocytosis, some microglia show enhanced glycolytic and oxidative phosphorylation (OXPHOS) programs. Under persistent pathological stress, increased glucose uptake may not translate into effective energy production and can coexist with inflammation and impaired lipid metabolism. In late disease, microglia with reduced metabolic capacity and impaired phagocytosis become more prevalent. However, higher expression of OXPHOS\u2010related genes in some microglial states associated with tau pathology does not necessarily indicate improved mitochondrial respiration. These population\u2010level patterns do not imply that individual microglia follow a fixed sequence of metabolic changes. Longitudinal cell tracking and microglia\u2010specific metabolic flux measurements are needed to test this model and inform interventions tailored to disease stage and microglial state.<\/jats:p>","DOI":"10.1002\/alz.71909","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T11:55:56Z","timestamp":1791546956000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spatiotemporal heterogeneity and dynamic evolution of microglial glucose metabolic reprogramming in Alzheimer's disease"],"prefix":"10.1002","volume":"22","author":[{"given":"Yuan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurology, Dongzhimen Hospital Beijing University of Chinese Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuyao","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine  Beijing 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