Authors
Yuan Chen, Fuyao Li, Junlei Zhang, Mingqing Wei, Jingnian Ni, Ting Li, Lulu Yao, Jinzhou Tian, Jing Shi
Published in
Alzheimer's & dementia : the journal of the Alzheimer's Association. Volume 22. Issue 10. Pages e71909.
Abstract
Alzheimer's disease (AD) is accompanied by persistent disturbances in brain energy metabolism, and microglial glucose metabolic reprogramming constitutes an important link among pathological protein deposition, neuroinflammation, and impaired clearance. This review examines these metabolic changes across disease stages, brain regions, and plaque-associated microenvironments and proposes a dynamic state-composition 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-related genes in some microglial states associated with tau pathology does not necessarily indicate improved mitochondrial respiration. These population-level patterns do not imply that individual microglia follow a fixed sequence of metabolic changes. Longitudinal cell tracking and microglia-specific metabolic flux measurements are needed to test this model and inform interventions tailored to disease stage and microglial state.
PMID:
42851167
Bibliographic data and abstract were imported from PubMed on 09 Oct 2026.
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