Home > Publications database > Spatial proteomics of Alzheimer's disease-specific human microglial states. > print

001     303091
005     20250731105626.0
024 7 _ |a 10.1038/s41590-025-02203-w
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024 7 _ |a 1529-2908
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024 7 _ |a 1529-2916
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037 _ _ |a DKFZ-2025-01516
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Mrdjen, Dunja
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245 _ _ |a Spatial proteomics of Alzheimer's disease-specific human microglial states.
260 _ _ |a London
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|b Springer Nature Limited
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500 _ _ |a 2025 Aug;26(8):1397-1410
520 _ _ |a 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.
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700 1 _ |a Cannon, Bryan J
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700 1 _ |a Amouzgar, Meelad
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700 1 _ |a Kim, YeEun
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700 1 _ |a Liu, Candace
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700 1 _ |a Vijayaragavan, Kausalia
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700 1 _ |a Camacho, Christine
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700 1 _ |a Spence, Angie
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700 1 _ |a McCaffrey, Erin F
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700 1 _ |a Bharadwaj, Anusha
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700 1 _ |a Tebaykin, Dmitry
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700 1 _ |a Bukhari, Syed
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700 1 _ |a Bosse, Marc
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700 1 _ |a Hartmann, Felix
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700 1 _ |a Kagel, Adam
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700 1 _ |a Oliveria, John Paul
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700 1 _ |a Yakabi, Koya
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700 1 _ |a Serrano, Geidy E
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700 1 _ |a Corrada, Maria M
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700 1 _ |a Kawas, Claudia H
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700 1 _ |a Tibshirani, Robert
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700 1 _ |a Beach, Thomas G
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700 1 _ |a Corces, M Ryan
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700 1 _ |a Greenleaf, Will
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700 1 _ |a Angelo, R Michael
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700 1 _ |a Montine, Thomas
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700 1 _ |a Bendall, Sean C
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773 _ _ |a 10.1038/s41590-025-02203-w
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