Calibrating microglia states in Alzheimer’s disease: decoding immune-metabolic networks and nano-targeted multicomponent therapies

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Alzheimer's disease treatment is evolving from pathology removal to regulating the brain microenvironment and microglial states.
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Anti-Aβ monoclonal antibodies like lecanemab and donanemab show disease-modifying effects but limited cognitive benefits and safety risks.
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Microglia are central to Alzheimer's disease, influenced by genetic, sex, and environmental factors, and are active determinants of disease progression.
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Three key drivers of microglial dysfunction include the TREM2–APOE axis, complement-mediated synaptic elimination, and immunometabolic reprogramming.
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Future therapies should integrate both pathology removal and microenvironment protection, tailored by disease stage and microglial state.

Frontiers In Immunology

by Jin Feng Xing, Kaijin Mu, Xue Yan, Xu Yang, Dongnan Zhang, Wanning Gao, Tengyue Zhang, Shuangying Yang, Runze Wang, Weimin Zhang, Yilong Zhu
June 16, 2026

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