TY  - JOUR
AU  - Mrdjen, Dunja
AU  - Cannon, Bryan J
AU  - Amouzgar, Meelad
AU  - Kim, YeEun
AU  - Liu, Candace
AU  - Vijayaragavan, Kausalia
AU  - Camacho, Christine
AU  - Spence, Angie
AU  - McCaffrey, Erin F
AU  - Bharadwaj, Anusha
AU  - Tebaykin, Dmitry
AU  - Bukhari, Syed
AU  - Bosse, Marc
AU  - Hartmann, Felix
AU  - Kagel, Adam
AU  - Oliveria, John Paul
AU  - Yakabi, Koya
AU  - Serrano, Geidy E
AU  - Corrada, Maria M
AU  - Kawas, Claudia H
AU  - Tibshirani, Robert
AU  - Beach, Thomas G
AU  - Corces, M Ryan
AU  - Greenleaf, Will
AU  - Angelo, R Michael
AU  - Montine, Thomas
AU  - Bendall, Sean C
TI  - Spatial proteomics of Alzheimer's disease-specific human microglial states.
JO  - Nature immunology
VL  - 26
IS  - 8
SN  - 1529-2908
CY  - London
PB  - Springer Nature Limited
M1  - DKFZ-2025-01516
SP  - 1397-1410
PY  - 2025
N1  - 2025 Aug;26(8):1397-1410
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:40696045
DO  - DOI:10.1038/s41590-025-02203-w
UR  - https://inrepo02.dkfz.de/record/303091
ER  -