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000303091 1001_ $$aMrdjen, Dunja$$b0
000303091 245__ $$aSpatial proteomics of Alzheimer's disease-specific human microglial states.
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000303091 520__ $$aMicroglia 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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000303091 7001_ $$aCannon, Bryan J$$b1
000303091 7001_ $$00000-0003-0521-9223$$aAmouzgar, Meelad$$b2
000303091 7001_ $$aKim, YeEun$$b3
000303091 7001_ $$aLiu, Candace$$b4
000303091 7001_ $$aVijayaragavan, Kausalia$$b5
000303091 7001_ $$00000-0002-4924-591X$$aCamacho, Christine$$b6
000303091 7001_ $$aSpence, Angie$$b7
000303091 7001_ $$aMcCaffrey, Erin F$$b8
000303091 7001_ $$aBharadwaj, Anusha$$b9
000303091 7001_ $$00000-0003-0913-8834$$aTebaykin, Dmitry$$b10
000303091 7001_ $$aBukhari, Syed$$b11
000303091 7001_ $$00000-0003-4912-8059$$aBosse, Marc$$b12
000303091 7001_ $$0P:(DE-He78)5cbf51db82a42b08a814f47dbc9412ca$$aHartmann, Felix$$b13$$udkfz
000303091 7001_ $$aKagel, Adam$$b14
000303091 7001_ $$aOliveria, John Paul$$b15
000303091 7001_ $$aYakabi, Koya$$b16
000303091 7001_ $$aSerrano, Geidy E$$b17
000303091 7001_ $$aCorrada, Maria M$$b18
000303091 7001_ $$aKawas, Claudia H$$b19
000303091 7001_ $$aTibshirani, Robert$$b20
000303091 7001_ $$aBeach, Thomas G$$b21
000303091 7001_ $$00000-0001-7465-7652$$aCorces, M Ryan$$b22
000303091 7001_ $$00000-0003-1409-3095$$aGreenleaf, Will$$b23
000303091 7001_ $$00000-0003-1531-5067$$aAngelo, R Michael$$b24
000303091 7001_ $$00000-0002-1346-2728$$aMontine, Thomas$$b25
000303091 7001_ $$00000-0003-1341-2453$$aBendall, Sean C$$b26
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