Nature Immunology, Published online: 24 July 2025; doi:10.1038/s41590-025-02205-8

Single-cell spatial proteomics paired with chromatin accessibility mapping identifies a diverse range of human microglial immune states. In Alzheimer’s disease, hippocampal microglia tend to lose antigen-presenting function and become disengaged from inhibitory synapses. Our dual-modality approach illustrates the importance of integrating local tissue architecture and cell identity to fully understand disease-associated immune remodeling.



Summary

A new study published in Nature Immunology combines single-cell spatial proteomics and chromatin accessibility mapping to uncover diverse microglial immune states in human tissue. The research, focused on Alzheimer’s disease, reveals that hippocampal microglia lose their ability to present antigens and detach from inhibitory synapses within the brain. This innovative dual-modality approach highlights the critical role of understanding local tissue context and individual cell identity when investigating immune system changes associated with disease. The findings underscore the necessity of integrating spatial and cellular information for a comprehensive understanding of immune remodeling.

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