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000285462 1001_ $$0P:(DE-2719)9002289$$aFeiten, Astrid Feentje$$b0$$eFirst author$$udzne
000285462 245__ $$aTREM2 expression level is critical for microglial state, metabolic capacity and efficacy of TREM2 agonism.
000285462 260__ $$a[London]$$bSpringer Nature$$c2026
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000285462 520__ $$aTriggering receptor expressed on myeloid cells 2 (TREM2) is a central regulator of microglial activity and loss-of-function coding variants are major risk factors for late onset Alzheimer's disease (LOAD). To better understand the molecular and functional changes associated with TREM2 signalling in microglia, we generated a TREM2 reporter mouse. In APP transgenic animals, bulk RNA-sequencing of isolated microglia sorted based on reporter expression highlighted TREM2 level-related changes in major immunometabolic pathways, and enrichment of genes in oxidative phosphorylation and cholesterol metabolism in microglia with increased TREM2 expression. Metabolic and lipidomic profiling of sorted microglia showed that, independent of Aβ pathology, TREM2 expression correlated with signatures consistent with increased cellular redox, energetics, and cholesterol homoeostasis. In accordance, metabolic activity correlated with phagocytic capacity. Finally, we performed chronic treatment with a TREM2 agonist antibody and identified a window of TREM2 expression where microglia are most responsive, thereby informing clinical applications of TREM2 agonists.
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000285462 7001_ $$0P:(DE-2719)9001875$$aDahm, Kilian$$b1$$eFirst author
000285462 7001_ $$0P:(DE-2719)2812546$$aSchlepckow, Kai$$b2$$eFirst author
000285462 7001_ $$avan Lengerich, Bettina$$b3
000285462 7001_ $$00000-0001-8119-326X$$aSuh, Jung H$$b4
000285462 7001_ $$aReifschneider, Anika$$b5
000285462 7001_ $$0P:(DE-2719)2810988$$aWefers, Benedikt$$b6
000285462 7001_ $$aBartos, Laura M$$b7
000285462 7001_ $$0P:(DE-2719)9001653$$aWind, Karin$$b8$$udzne
000285462 7001_ $$0P:(DE-2719)9001304$$ade Weerd, Lis$$b9
000285462 7001_ $$0P:(DE-2719)9000845$$aUlas, Thomas$$b10$$udzne
000285462 7001_ $$0P:(DE-2719)9000846$$aDe-Domenico, Elena$$b11
000285462 7001_ $$0P:(DE-2719)9002695$$aGrundschöttel, Pia$$b12$$udzne
000285462 7001_ $$0P:(DE-2719)9002116$$aPaulusch, Stefan$$b13$$udzne
000285462 7001_ $$aTast, Benjamin$$b14
000285462 7001_ $$00000-0001-5654-1162$$aHonda, Tamisa$$b15
000285462 7001_ $$0P:(DE-2719)2810938$$aMüller, Stephan A$$b16
000285462 7001_ $$0P:(DE-2719)2812750$$aBecker, Matthias$$b17
000285462 7001_ $$00000-0003-1041-5747$$aKhalin, Igor$$b18
000285462 7001_ $$00000-0002-3051-8113$$aRicci, Alessio$$b19
000285462 7001_ $$00000-0002-9069-2594$$aLiesz, Arthur$$b20
000285462 7001_ $$0P:(DE-2719)2810716$$aBrunner, Bettina$$b21$$udzne
000285462 7001_ $$0P:(DE-2719)9002298$$aKrenner, Claudia$$b22$$udzne
000285462 7001_ $$0P:(DE-2719)9002284$$aBuschmann, Katrin$$b23$$udzne
000285462 7001_ $$0P:(DE-2719)9000236$$aNuscher, Brigitte$$b24
000285462 7001_ $$0P:(DE-2719)9002306$$aSpieth, Lena$$b25$$udzne
000285462 7001_ $$0P:(DE-2719)9003939$$aJunker, Niklas$$b26$$udzne
000285462 7001_ $$0P:(DE-2719)9001700$$aBerghoff, Stefan A$$b27$$udzne
000285462 7001_ $$aDavis, Sonnet S$$b28
000285462 7001_ $$0P:(DE-2719)2811021$$aNeher, Jonas J$$b29
000285462 7001_ $$0P:(DE-2719)2000028$$aWurst, Wolfgang$$b30
000285462 7001_ $$0P:(DE-2719)9000853$$aPlesnila, Nikolaus$$b31
000285462 7001_ $$00000-0003-3012-7881$$aLewcock, Joseph W$$b32
000285462 7001_ $$0P:(DE-2719)2811642$$aSimons, Mikael$$b33
000285462 7001_ $$0P:(DE-2719)2181459$$aLichtenthaler, Stefan F$$b34
000285462 7001_ $$00000-0003-1032-1265$$aDi Paolo, Gilbert$$b35
000285462 7001_ $$0P:(DE-2719)9001539$$aBrendel, Matthias$$b36
000285462 7001_ $$0P:(DE-2719)9000368$$aCapell, Anja$$b37
000285462 7001_ $$00000-0002-6901-1176$$aMonroe, Kathryn M$$b38
000285462 7001_ $$0P:(DE-2719)2811660$$aSchultze, Joachim L$$b39
000285462 7001_ $$0P:(DE-2719)2202037$$aHaass, Christian$$b40$$eLast author
000285462 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-026-68706-8$$gVol. 17, no. 1, p. 2002$$n1$$p2002$$tNature Communications$$v17$$x2041-1723$$y2026
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