Research BriefingPublished: 24 July 2025Nature Immunology (2025)Cite this articleSubjectsBiotechnologyNeuroimmunologySingle-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.This is a preview of subscription content, access via your institutionAccess optionsAccess Nature and 54 other Nature Portfolio journalsGet Nature+, our best-value online-access subscription27,99 € / 30 dayscancel any timeLearn moreSubscribe to this journalReceive 12 print issues and online access209,00 € per yearonly 17,42 € per issueLearn moreBuy this articlePurchase on SpringerLinkInstant access to full article PDFBuy nowPrices may be subject to local taxes which are calculated during checkoutFig. 1: Immune activation continuum of hippocampal microglia is perturbed in Alzheimer’s disease.ReferencesPrinz, M., Jung, S. & Priller, J. Microglia biology: one century of evolving concepts. Cell 179, 292–311 (2019). A comprehensive review charting the historical and conceptual development of microglial research.CAS PubMed Google Scholar Keren-Shaul, H. et al. A unique microglia type associated with restricting development of Alzheimer’s disease. Cell 169, 1276–1290.e17 (2017). Seminal primary study that first defined disease-associated microglia and highlighted subtype heterogeneity in Alzheimer’s disease.CAS PubMed Google Scholar Vijayaragavan, K. et al. Single-cell spatial proteomic imaging for human neuropathology. Acta Neuropathol. Commun. 10, 158 (2022). Peer-reviewed protocol and dataset describing the MIBI workflow for high-plex in situ proteomics of human brain tissue.PubMed PubMed Central Google Scholar Mrdjen, D. et al. High-dimensional single-cell mapping of central nervous system immune cells reveals distinct myeloid subsets in health, aging and disease. Immunity 48, 380–395.e6 (2018). This paper introduced mass cytometry-based single-cell proteomics to profile immune diversity in the central nervous system, inspiring the continuum approach.CAS PubMed Google Scholar Corces, M. R. et al. Single-cell epigenomic analyses implicate causal variants at inherited risk loci for Alzheimer’s and Parkinson’s diseases. Nat. Genet. 52, 1158–1168 (2020). This paper provides the single-nucleus ATAC-seq dataset and analytical framework we used to construct the epigenetic continuum.CAS PubMed PubMed Central Google Scholar Download referencesAdditional informationPublisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.This is a summary of: Mrdjen, D. et al. Spatial proteomics reveals Alzheimer’s disease-specific human microglial states. Nat. Immunol. https://doi.org/10.1038/s41590-025-02203-w (2025).Rights and permissionsReprints and permissionsAbout this article