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000904376 1001_ $$0P:(DE-HGF)0$$aXiang, Xianyuan$$b0$$eCorresponding author
000904376 245__ $$aMicroglial activation states drive glucose uptake and FDG-PET alterations in neurodegenerative diseases
000904376 260__ $$aWashington, DC$$bAAAS$$c2021
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000904376 520__ $$a2-Deoxy-2-[18F]fluoro-d-glucose positron emission tomography (FDG-PET) is widely used to study cerebral glucose metabolism. Here, we investigated whether the FDG-PET signal is directly influenced by microglial glucose uptake in mouse models and patients with neurodegenerative diseases. Using a recently developed approach for cell sorting after FDG injection, we found that, at cellular resolution, microglia displayed higher glucose uptake than neurons and astrocytes. Alterations in microglial glucose uptake were responsible for both the FDG-PET signal decrease in Trem2-deficient mice and the FDG-PET signal increase in mouse models for amyloidosis. Thus, opposite microglial activation states determine the differential FDG uptake. Consistently, 12 patients with Alzheimer’s disease and 21 patients with four-repeat tauopathies also exhibited a positive association between glucose uptake and microglial activity as determined by 18F-GE-180 18-kDa translocator protein PET (TSPO-PET) in preserved brain regions, indicating that the cerebral glucose uptake in humans is also strongly influenced by microglial activity. Our findings suggest that microglia activation states are responsible for FDG-PET signal alterations in patients with neurodegenerative diseases and mouse models for amyloidosis. Microglial activation states should therefore be considered when performing FDG-PET.
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000904376 7001_ $$0P:(DE-HGF)0$$aWind, Karin$$b1
000904376 7001_ $$0P:(DE-HGF)0$$aWiedemann, Thomas$$b2
000904376 7001_ $$0P:(DE-HGF)0$$aBlume, Tanja$$b3
000904376 7001_ $$0P:(DE-HGF)0$$aShi, Yuan$$b4
000904376 7001_ $$0P:(DE-HGF)0$$aBriel, Nils$$b5
000904376 7001_ $$0P:(DE-HGF)0$$aBeyer, Leonie$$b6
000904376 7001_ $$0P:(DE-HGF)0$$aBiechele, Gloria$$b7
000904376 7001_ $$0P:(DE-HGF)0$$aEckenweber, Florian$$b8
000904376 7001_ $$0P:(DE-HGF)0$$aZatcepin, Artem$$b9
000904376 7001_ $$0P:(DE-HGF)0$$aLammich, Sven$$b10
000904376 7001_ $$0P:(DE-HGF)0$$aRibicic, Sara$$b11
000904376 7001_ $$0P:(DE-HGF)0$$aTahirovic, Sabina$$b12
000904376 7001_ $$0P:(DE-HGF)0$$aWillem, Michael$$b13
000904376 7001_ $$0P:(DE-HGF)0$$aDeussing, Maximilian$$b14
000904376 7001_ $$0P:(DE-HGF)0$$aPalleis, Carla$$b15
000904376 7001_ $$0P:(DE-HGF)0$$aRauchmann, Boris-Stephan$$b16
000904376 7001_ $$0P:(DE-HGF)0$$aGildehaus, Franz-Josef$$b17
000904376 7001_ $$0P:(DE-HGF)0$$aLindner, Simon$$b18
000904376 7001_ $$0P:(DE-HGF)0$$aSpitz, Charlotte$$b19
000904376 7001_ $$0P:(DE-HGF)0$$aFranzmeier, Nicolai$$b20
000904376 7001_ $$0P:(DE-HGF)0$$aBaumann, Karlheinz$$b21
000904376 7001_ $$0P:(DE-HGF)0$$aRominger, Axel$$b22
000904376 7001_ $$0P:(DE-HGF)0$$aBartenstein, Peter$$b23
000904376 7001_ $$0P:(DE-HGF)0$$aZiegler, Sibylle$$b24
000904376 7001_ $$0P:(DE-Juel1)177611$$aDrzezga, Alexander$$b25
000904376 7001_ $$0P:(DE-HGF)0$$aRespondek, Gesine$$b26
000904376 7001_ $$0P:(DE-HGF)0$$aBuerger, Katharina$$b27
000904376 7001_ $$0P:(DE-HGF)0$$aPerneczky, Robert$$b28
000904376 7001_ $$0P:(DE-HGF)0$$aLevin, Johannes$$b29
000904376 7001_ $$0P:(DE-HGF)0$$aHöglinger, Günter U.$$b30
000904376 7001_ $$0P:(DE-HGF)0$$aHerms, Jochen$$b31
000904376 7001_ $$0P:(DE-HGF)0$$aHaass, Christian$$b32
000904376 7001_ $$0P:(DE-HGF)0$$aBrendel, Matthias$$b33
000904376 773__ $$0PERI:(DE-600)2518839-2$$a10.1126/scitranslmed.abe5640$$gVol. 13, no. 615, p. eabe5640$$n615$$peabe5640$$tScience translational medicine$$v13$$x1946-6234$$y2021
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000904376 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a  CAS Key Laboratory of Brain Connectome and Manipulation, Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, 518055 Shenzhen, China$$b0
000904376 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, 81377 Munich, Germany$$b1
000904376 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a German Center for Neurodegenerative Diseases (DZNE) Munich, 81377 Munich, Germany$$b1
000904376 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, 81377 Munich, Germany$$b2
000904376 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, 81377 Munich, Germany$$b3
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000904376 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a German Center for Neurodegenerative Diseases (DZNE) Munich, 81377 Munich, Germany$$b4
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000904376 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a Center for Neuropathology and Prion Research, Ludwig-Maximilians-University München, 81377 Munich, Germany$$b5
000904376 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$aDepartment of Nuclear Medicine, University Hospital of Munich, LMU Munich, 81377 Munich, Germany$$b6
000904376 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, 81377 Munich, Germany$$b7
000904376 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, 81377 Munich, Germany$$b8
000904376 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, 81377 Munich, Germany$$b9
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000904376 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a Department of Psychiatry and Psychotherapy, University Hospital of Munich, LMU Munich, 81377 Munich, Germany$$b16
000904376 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a Department of Radiology, University Hospital of Munich, LMU Munich, 81377 Munich, Germany$$b16
000904376 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, 81377 Munich, Germany$$b17
000904376 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, 81377 Munich, Germany$$b18
000904376 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a  Institute of Biochemistry and Molecular Biology, University of Augsburg, 86159 Augsburg, Germany$$b19
000904376 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a Institute for Stroke and Dementia Research (ISD), University Hospital of Munich, LMU Munich, 81377 Munich, Germany$$b20
000904376 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a Roche, Pharma Research and Early Development, NORD DTA/Neuroscience Discovery, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, CH-4070 Basel, Switzerland$$b21
000904376 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a  Department of Nuclear Medicine, University of Bern, Inselspital, CH-3010 Bern, Switzerland$$b22
000904376 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, 81377 Munich, Germany$$b22
000904376 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany$$b23
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000904376 9101_ $$0I:(DE-HGF)0$$6P:(DE-Juel1)177611$$a German Center for Neurodegenerative Diseases (DZNE) Bonn-Cologne, 53127 Bonn, Germany$$b25
000904376 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a Department of Neurology, Hannover Medical School, 30625 Hannover, Germany$$b26
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000904376 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a  Institute for Stroke and Dementia Research (ISD), University Hospital of Munich, LMU Munich, 81377 Munich, Germany$$b27
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000904376 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a Department of Psychiatry and Psychotherapy, University Hospital of Munich, LMU Munich, 81377 Munich, Germany$$b28
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000904376 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a Ageing Epidemiology (AGE) Research Unit, School of Public Health, Imperial College, London SW7 2AZ, UK$$b28
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