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@ARTICLE{Mrdjen:303091,
author = {D. Mrdjen and B. J. Cannon and M. Amouzgar and Y. Kim and
C. Liu and K. Vijayaragavan and C. Camacho and A. Spence and
E. F. McCaffrey and A. Bharadwaj and D. Tebaykin and S.
Bukhari and M. Bosse and F. Hartmann$^*$ and A. Kagel and J.
P. Oliveria and K. Yakabi and G. E. Serrano and M. M.
Corrada and C. H. Kawas and R. Tibshirani and T. G. Beach
and M. R. Corces and W. Greenleaf and R. M. Angelo and T.
Montine and S. C. Bendall},
title = {{S}patial proteomics of {A}lzheimer's disease-specific
human microglial states.},
journal = {Nature immunology},
volume = {26},
number = {8},
issn = {1529-2908},
address = {London},
publisher = {Springer Nature Limited},
reportid = {DKFZ-2025-01516},
pages = {1397-1410},
year = {2025},
note = {2025 Aug;26(8):1397-1410},
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.},
cin = {D260},
ddc = {610},
cid = {I:(DE-He78)D260-20160331},
pnm = {314 - Immunologie und Krebs (POF4-314)},
pid = {G:(DE-HGF)POF4-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40696045},
doi = {10.1038/s41590-025-02203-w},
url = {https://inrepo02.dkfz.de/record/303091},
}