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<p>Disease-associated microglial states are thought to contribute to Alzheimer’s disease (AD) progression, but characterizing them and their relationships to pathology remains challenging. Here we introduce CODEX-CNS—a multiplexed protein imaging technology with a custom data analysis pipeline for use in human brain samples. We profiled 704,706 cells in samples from the frontal cortex of 8 people with AD and 8 healthy controls and mapped features including blood–brain barrier, meningeal components and cell–cell interactions within the same tissue sections. Amongst the myeloid cell populations we identified, we found a border-associated macrophage-like microglial subset associated with aging. Further classifying myeloid cell subsets based on their spatial neighborhood, we identified a border-associated macrophage-like microglial subpopulation that was associated significantly with dense amyloid-β plaques, which we termed human plaque-associated microglia. This work offers insights into myeloid cell heterogeneity in AD and provides a new spatial approach to characterizing brain cells at the single-cell protein level.</p>

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Spatial proteomic analysis in human Alzheimer’s disease brains enables identification of microenvironment-dependent microglial cell states

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月18日

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  • Paula Sanchez-Molina,
  • Dennis-Dominik Rosmus,
  • Dillon Brownell,
  • Mert Meral,
  • Cavanagh Gohlich,
  • Aditya Pratapa,
  • Yaser Peymanfar,
  • Alyssa Whitley,
  • Yue Hou,
  • Nadezhda Nikulina,
  • Alina Bogachuk,
  • Ellen Lara Bouchard,
  • Aude Chiot,
  • Heidrun Kuhrt,
  • Peter Wieghofer,
  • Randall Woltjer,
  • Fabian Svara,
  • Oliver Braubach,
  • Bahareh Ajami

摘要

Disease-associated microglial states are thought to contribute to Alzheimer’s disease (AD) progression, but characterizing them and their relationships to pathology remains challenging. Here we introduce CODEX-CNS—a multiplexed protein imaging technology with a custom data analysis pipeline for use in human brain samples. We profiled 704,706 cells in samples from the frontal cortex of 8 people with AD and 8 healthy controls and mapped features including blood–brain barrier, meningeal components and cell–cell interactions within the same tissue sections. Amongst the myeloid cell populations we identified, we found a border-associated macrophage-like microglial subset associated with aging. Further classifying myeloid cell subsets based on their spatial neighborhood, we identified a border-associated macrophage-like microglial subpopulation that was associated significantly with dense amyloid-β plaques, which we termed human plaque-associated microglia. This work offers insights into myeloid cell heterogeneity in AD and provides a new spatial approach to characterizing brain cells at the single-cell protein level.