Journal Article

DKFZ-2025-01516

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Spatial proteomics of Alzheimer's disease-specific human microglial states.

Mrdjen, D. ; Cannon, B. J. ; Amouzgar, M. ; Kim, Y. ; Liu, C. ; Vijayaragavan, K. ; Camacho, C. ; Spence, A. ; McCaffrey, E. F. ; Bharadwaj, A. ; Tebaykin, D. ; Bukhari, S. ; Bosse, M. ; Hartmann, F.DKFZ* ; Kagel, A. ; Oliveria, J. P. ; Yakabi, K. ; Serrano, G. E. ; Corrada, M. M. ; Kawas, C. H. ; Tibshirani, R. ; Beach, T. G. ; Corces, M. R. ; Greenleaf, W. ; Angelo, R. M. ; Montine, T. ; Bendall, S. C.

2025
Springer Nature Limited London

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Please use a persistent id in citations: doi:10.1038/s41590-025-02203-w

Abstract: Microglia are implicated in aging, neurodegeneration and Alzheimer's disease (AD). Low-plex protein imaging does not capture cellular states and interactions in the human brain, which differs from rodent models. Here we used multiplexed ion beam imaging to spatially map cellular states and niches in cognitively normal human brains, identifying a spectrum of proteomic microglial profiles. Defined by immune activation states that were skewed across brain regions and compartmentalized according to microenvironments, this spectrum enables the identification of proteomic trends across the microglia of ten cognitively normal individuals and orthogonally with single-nuclei epigenetic analysis, revealing associated molecular functions. Notably, AD tissues exhibit regulatory shifts in the immunologically active cells at the end of the proteomic spectrum, including enrichment of CD33 and CD44 and decreases in HLA-DR, P2RY12 and ApoE expression. These findings establish an in situ, single-cell spatial proteomic framework for AD-specific microglial states.

Note: 2025 Aug;26(8):1397-1410

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Contributing Institute(s):

1. NWG Systemimmunologie und Einzelzell-Biologie (D260)

Research Program(s):

1. 314 - Immunologie und Krebs (POF4-314) (POF4-314)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Nature ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 30 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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