000271973 001__ 271973
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000271973 037__ $$aDZNE-2024-01115
000271973 041__ $$aEnglish
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000271973 1001_ $$0P:(DE-2719)9001654$$aZatcepin, Artem$$b0$$eFirst author
000271973 245__ $$aRegional desynchronization of microglial activity is associated with cognitive decline in Alzheimer's disease.
000271973 260__ $$aLondon$$bBiomed Central$$c2024
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000271973 520__ $$aMicroglial activation is one hallmark of Alzheimer disease (AD) neuropathology but the impact of the regional interplay of microglia cells in the brain is poorly understood. We hypothesized that microglial activation is regionally synchronized in the healthy brain but experiences regional desynchronization with ongoing neurodegenerative disease. We addressed the existence of a microglia connectome and investigated microglial desynchronization as an AD biomarker.To validate the concept, we performed microglia depletion in mice to test whether interregional correlation coefficients (ICCs) of 18 kDa translocator protein (TSPO)-PET change when microglia are cleared. Next, we evaluated the influence of dysfunctional microglia and AD pathophysiology on TSPO-PET ICCs in the mouse brain, followed by translation to a human AD-continuum dataset. We correlated a personalized microglia desynchronization index with cognitive performance. Finally, we performed single-cell radiotracing (scRadiotracing) in mice to ensure the microglial source of the measured desynchronization.Microglia-depleted mice showed a strong ICC reduction in all brain compartments, indicating microglia-specific desynchronization. AD mouse models demonstrated significant reductions of microglial synchronicity, associated with increasing variability of cellular radiotracer uptake in pathologically altered brain regions. Humans within the AD-continuum indicated a stage-depended reduction of microglia synchronicity associated with cognitive decline. scRadiotracing in mice showed that the increased TSPO signal was attributed to microglia.Using TSPO-PET imaging of mice with depleted microglia and scRadiotracing in an amyloid model, we provide first evidence that a microglia connectome can be assessed in the mouse brain. Microglia synchronicity is closely associated with cognitive decline in AD and could serve as an independent personalized biomarker for disease progression.
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000271973 650_7 $$2Other$$aAlzheimer’s disease
000271973 650_7 $$2Other$$aBrain connectivity
000271973 650_7 $$2Other$$aDementia
000271973 650_7 $$2Other$$aMicroglia
000271973 650_7 $$2Other$$aMicroglia desynchronization
000271973 650_7 $$2Other$$aMicroglia synchronicity
000271973 650_7 $$2Other$$aNeuroinflammation
000271973 650_7 $$2Other$$aPET
000271973 650_7 $$2Other$$aTSPO
000271973 650_7 $$2NLM Chemicals$$aReceptors, GABA
000271973 650_2 $$2MeSH$$aAnimals
000271973 650_2 $$2MeSH$$aMicroglia: metabolism
000271973 650_2 $$2MeSH$$aAlzheimer Disease: metabolism
000271973 650_2 $$2MeSH$$aAlzheimer Disease: pathology
000271973 650_2 $$2MeSH$$aMice
000271973 650_2 $$2MeSH$$aCognitive Dysfunction: metabolism
000271973 650_2 $$2MeSH$$aHumans
000271973 650_2 $$2MeSH$$aBrain: metabolism
000271973 650_2 $$2MeSH$$aBrain: pathology
000271973 650_2 $$2MeSH$$aDisease Models, Animal
000271973 650_2 $$2MeSH$$aPositron-Emission Tomography
000271973 650_2 $$2MeSH$$aReceptors, GABA: metabolism
000271973 650_2 $$2MeSH$$aMale
000271973 650_2 $$2MeSH$$aMice, Transgenic
000271973 650_2 $$2MeSH$$aConnectome: methods
000271973 650_2 $$2MeSH$$aFemale
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000271973 7001_ $$0P:(DE-2719)9001652$$aGnörich, Johannes$$b1$$udzne
000271973 7001_ $$0P:(DE-2719)9001808$$aRauchmann, Boris Stephan$$b2$$udzne
000271973 7001_ $$aBartos, Laura M$$b3
000271973 7001_ $$aWagner, Stephan$$b4
000271973 7001_ $$aFranzmeier, Nicolai$$b5
000271973 7001_ $$aMalpetti, Maura$$b6
000271973 7001_ $$aXiang, Xianyuan$$b7
000271973 7001_ $$0P:(DE-2719)2811433$$aShi, Yuan$$b8$$udzne
000271973 7001_ $$aParhizkar, Samira$$b9
000271973 7001_ $$aGrosch, Maximilian$$b10
000271973 7001_ $$0P:(DE-2719)9001653$$aWind-Mark, Karin$$b11$$udzne
000271973 7001_ $$aKunte, Sebastian T$$b12
000271973 7001_ $$aBeyer, Leonie$$b13
000271973 7001_ $$0P:(DE-2719)9001221$$aKlaus, Carolin$$b14$$udzne
000271973 7001_ $$0P:(DE-2719)9000502$$aBrösamle, Desirée$$b15$$udzne
000271973 7001_ $$0P:(DE-2719)2814015$$aWendeln, Ann-Christin$$b16
000271973 7001_ $$0P:(DE-2719)2813660$$aOsei-Sarpong, Collins$$b17$$udzne
000271973 7001_ $$aHeindl, Steffanie$$b18
000271973 7001_ $$aLiesz, Arthur$$b19
000271973 7001_ $$aStoecklein, Sophia$$b20
000271973 7001_ $$aBiechele, Gloria$$b21
000271973 7001_ $$aFinze, Anika$$b22
000271973 7001_ $$aEckenweber, Florian$$b23
000271973 7001_ $$aLindner, Simon$$b24
000271973 7001_ $$aRominger, Axel$$b25
000271973 7001_ $$aBartenstein, Peter$$b26
000271973 7001_ $$aWillem, Michael$$b27
000271973 7001_ $$0P:(DE-2719)2442036$$aTahirovic, Sabina$$b28$$udzne
000271973 7001_ $$0P:(DE-2719)2810441$$aHerms, Jochen$$b29$$udzne
000271973 7001_ $$0P:(DE-2719)2811351$$aBuerger, Katharina$$b30$$udzne
000271973 7001_ $$0P:(DE-2719)2811642$$aSimons, Mikael$$b31$$udzne
000271973 7001_ $$0P:(DE-2719)2202037$$aHaass, Christian$$b32$$udzne
000271973 7001_ $$aRupprecht, Rainer$$b33
000271973 7001_ $$aRiemenschneider, Markus J$$b34
000271973 7001_ $$aAlbert, Nathalie L$$b35
000271973 7001_ $$0P:(DE-2719)2812219$$aBeyer, Marc$$b36$$udzne
000271973 7001_ $$0P:(DE-2719)2811021$$aNeher, Jonas J$$b37$$udzne
000271973 7001_ $$0P:(DE-2719)9002242$$aPaeger, Lars$$b38$$udzne
000271973 7001_ $$0P:(DE-2719)2811659$$aLevin, Johannes$$b39$$udzne
000271973 7001_ $$0P:(DE-2719)2811373$$aHöglinger, Günter U$$b40$$udzne
000271973 7001_ $$0P:(DE-2719)2812234$$aPerneczky, Robert$$b41$$udzne
000271973 7001_ $$aZiegler, Sibylle I$$b42
000271973 7001_ $$0P:(DE-2719)9001539$$aBrendel, Matthias$$b43$$eLast author$$udzne
000271973 773__ $$0PERI:(DE-600)2244557-2$$a10.1186/s13024-024-00752-6$$gVol. 19, no. 1, p. 64$$n1$$p64$$tMolecular neurodegeneration$$v19$$x1750-1326$$y2024
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