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Nat Neurosci2026;29(7):1599-1614.July 1, 2026Journal Article

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

Paula Sanchez-Molina1,2, Dennis-Dominik Rosmus3,4,5, Dillon Brownell1,2, Mert Meral6, Cavanagh Gohlich1,2, Aditya Pratapa7, Yaser Peymanfar7, Alyssa Whitley7, Yue Hou7, Nadezhda Nikulina7, Alina Bogachuk1,2, Ellen Lara Bouchard1,2, Aude Chiot1,2, Heidrun Kuhrt3, Peter Wieghofer3,4, Randall Woltjer8, Fabian Svara6, Oliver Braubach9, Bahareh Ajami10,11,12
1Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR, USA.
2Department of Behavioral and Systems Neuroscience, Oregon Health and Science University, Portland, OR, USA.
3Institute of Anatomy, Leipzig University, Leipzig, Germany.
4Cellular Neuroanatomy, Chair of Anatomy and Cell Biology, Institute of Theoretical Medicine, University of Augsburg, Augsburg, Germany.
5Department of Neurology, Leipzig University Medical Center, Leipzig, Germany.
6ariadne.ai AG, Lucerne, Switzerland.
7Akoya Biosciences, Marlborough, MA, USA.
8Department of Pathology, Oregon Health and Science University, Portland, OR, USA.
9Akoya Biosciences, Marlborough, MA, USA. obraubach@icloud.com.
10Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR, USA. ajami@ohsu.edu.
11Department of Behavioral and Systems Neuroscience, Oregon Health and Science University, Portland, OR, USA. ajami@ohsu.edu.
12Department of Neurology and Regenerative Medicine Institute, Cedars Sinai, Los Angeles, CA, USA. ajami@ohsu.edu.
PubMed PMC DOI PDF

Abstract

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 wit…

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