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000165257 0247_ $$2doi$$a10.1002/ana.26465
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000165257 037__ $$aDZNE-2022-01550
000165257 041__ $$aEnglish
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000165257 1001_ $$0P:(DE-2719)9001808$$aRauchmann, Boris Stephan$$b0$$eFirst author$$udzne
000165257 245__ $$aMicroglial Activation and Connectivity in Alzheimer Disease and Aging.
000165257 260__ $$aHoboken, NJ$$bWiley-Blackwell$$c2022
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000165257 520__ $$aAlzheimer disease (AD) is characterized by amyloid β (Aβ) plaques and neurofibrillary tau tangles, but increasing evidence suggests that neuroinflammation also plays a key role, driven by the activation of microglia. Aβ and tau pathology appear to spread along pathways of highly connected brain regions, but it remains elusive whether microglial activation follows a similar distribution pattern. Here, we assess whether connectivity is associated with microglia activation patterns.We included 32 Aβ-positive early AD subjects (18 women, 14 men) and 18 Aβ-negative age-matched healthy controls (10 women, 8 men) from the prospective ActiGliA (Activity of Cerebral Networks, Amyloid and Microglia in Aging and Alzheimer's Disease) study. All participants underwent microglial activation positron emission tomography (PET) with the third-generation mitochondrial 18 kDa translocator protein (TSPO) ligand [18 F]GE-180 and magnetic resonance imaging (MRI) to measure resting-state functional and structural connectivity.We found that inter-regional covariance in TSPO-PET and standardized uptake value ratio was preferentially distributed along functionally highly connected brain regions, with MRI structural connectivity showing a weaker association with microglial activation. AD patients showed increased TSPO-PET tracer uptake bilaterally in the anterior medial temporal lobe compared to controls, and higher TSPO-PET uptake was associated with cognitive impairment and dementia severity in a disease stage-dependent manner.Microglial activation distributes preferentially along highly connected brain regions, similar to tau pathology. These findings support the important role of microglia in neurodegeneration, and we speculate that pathology spreads throughout the brain along vulnerable connectivity pathways. ANN NEUROL 2022.
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000165257 650_7 $$2NLM Chemicals$$aAmyloid beta-Peptides
000165257 650_7 $$2NLM Chemicals$$atau Proteins
000165257 650_7 $$2NLM Chemicals$$aLigands
000165257 650_7 $$2NLM Chemicals$$aTSPO protein, human
000165257 650_7 $$2NLM Chemicals$$aReceptors, GABA
000165257 650_2 $$2MeSH$$aMale
000165257 650_2 $$2MeSH$$aHumans
000165257 650_2 $$2MeSH$$aFemale
000165257 650_2 $$2MeSH$$aAlzheimer Disease: pathology
000165257 650_2 $$2MeSH$$aAmyloid beta-Peptides: metabolism
000165257 650_2 $$2MeSH$$aMicroglia: metabolism
000165257 650_2 $$2MeSH$$atau Proteins: metabolism
000165257 650_2 $$2MeSH$$aLigands
000165257 650_2 $$2MeSH$$aProspective Studies
000165257 650_2 $$2MeSH$$aPositron-Emission Tomography: methods
000165257 650_2 $$2MeSH$$aPlaque, Amyloid: metabolism
000165257 650_2 $$2MeSH$$aBrain: pathology
000165257 650_2 $$2MeSH$$aReceptors, GABA: metabolism
000165257 7001_ $$0P:(DE-2719)9001539$$aBrendel, Matthias$$b1$$udzne
000165257 7001_ $$00000-0001-9736-2283$$aFranzmeier, Nicolai$$b2
000165257 7001_ $$aTrappmann, Lena$$b3
000165257 7001_ $$aZaganjori, Mirlind$$b4
000165257 7001_ $$aErsoezlue, Ersin$$b5
000165257 7001_ $$0P:(DE-2719)2812759$$aMorenas-Rodriguez, Estrella$$b6$$udzne
000165257 7001_ $$0P:(DE-2719)9001027$$aGuersel, Selim$$b7$$udzne
000165257 7001_ $$aBurow, Lena$$b8
000165257 7001_ $$0P:(DE-2719)9000176$$aKurz, Carolin$$b9$$udzne
000165257 7001_ $$aHaeckert, Jan$$b10
000165257 7001_ $$aTatò, Maia$$b11
000165257 7001_ $$0P:(DE-2719)9000381$$aUtecht, Julia$$b12$$udzne
000165257 7001_ $$aPapazov, Boris$$b13
000165257 7001_ $$aPogarell, Oliver$$b14
000165257 7001_ $$aJanowitz, Daniel$$b15
000165257 7001_ $$0P:(DE-2719)2811351$$aBürger, Katharina$$b16$$udzne
000165257 7001_ $$0P:(DE-2719)9000543$$aEwers, Michael$$b17$$udzne
000165257 7001_ $$0P:(DE-2719)9000852$$aPalleis, Carla$$b18$$udzne
000165257 7001_ $$0P:(DE-2719)9000882$$aWeidinger, Endy$$b19$$udzne
000165257 7001_ $$aBiechele, Gloria$$b20
000165257 7001_ $$aSchuster, Sebastian$$b21
000165257 7001_ $$aFinze, Anika$$b22
000165257 7001_ $$aEckenweber, Florian$$b23
000165257 7001_ $$aRupprecht, Rainer$$b24
000165257 7001_ $$0P:(DE-2719)9000971$$aRominger, Axel$$b25$$udzne
000165257 7001_ $$00000-0002-3841-3391$$aGoldhardt, Oliver$$b26
000165257 7001_ $$aGrimmer, Timo$$b27
000165257 7001_ $$aKeeser, Daniel$$b28
000165257 7001_ $$00000-0003-0325-4674$$aStoecklein, Sophia$$b29
000165257 7001_ $$aDietrich, Olaf$$b30
000165257 7001_ $$aBartenstein, Peter$$b31
000165257 7001_ $$0P:(DE-2719)2811659$$aLevin, Johannes$$b32$$udzne
000165257 7001_ $$0P:(DE-2719)2811373$$aHöglinger, Günter$$b33$$udzne
000165257 7001_ $$0P:(DE-2719)2812234$$aPerneczky, Robert$$b34$$eLast author$$udzne
000165257 773__ $$0PERI:(DE-600)2037912-2$$a10.1002/ana.26465$$gp. ana.26465$$n5$$p768 - 781$$tAnnals of neurology$$v92$$x0364-5134$$y2022
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