Xiang, Xianyuan ORCID: 0000-0002-8125-9027, Wind, Karin, Wiedemann, Thomas, Blume, Tanja, Shi, Yuan ORCID: 0000-0001-6135-1830, Briel, Nils, Beyer, Leonie ORCID: 0000-0002-7358-4495, Biechele, Gloria, Eckenweber, Florian, Zatcepin, Artem ORCID: 0000-0002-0224-088X, Lammich, Sven, Ribicic, Sara, Tahirovic, Sabina, Willem, Michael, Deussing, Maximilian, Palleis, Carla, Rauchmann, Boris-Stephan, Gildehaus, Franz-Josef, Lindner, Simon, Spitz, Charlotte, Franzmeier, Nicolai, Baumann, Karlheinz, Rominger, Axel, Bartenstein, Peter, Ziegler, Sibylle, Drzezga, Alexander, Respondek, Gesine, Buerger, Katharina, Perneczky, Robert, Levin, Johannes, Hoeglinger, Guenter U., Herms, Jochen, Haass, Christian and Brendel, Matthias (2021). Microglial activation states drive glucose uptake and FDG-PET alterations in neurodegenerative diseases. Sci. Transl. Med., 13 (615). WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE. ISSN 1946-6242

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Abstract

2-Deoxy-2-[F-18]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 F-18-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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Xiang, XianyuanUNSPECIFIEDorcid.org/0000-0002-8125-9027UNSPECIFIED
Wind, KarinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiedemann, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blume, TanjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shi, YuanUNSPECIFIEDorcid.org/0000-0001-6135-1830UNSPECIFIED
Briel, NilsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beyer, LeonieUNSPECIFIEDorcid.org/0000-0002-7358-4495UNSPECIFIED
Biechele, GloriaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eckenweber, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zatcepin, ArtemUNSPECIFIEDorcid.org/0000-0002-0224-088XUNSPECIFIED
Lammich, SvenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ribicic, SaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tahirovic, SabinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Willem, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Deussing, MaximilianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Palleis, CarlaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rauchmann, Boris-StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gildehaus, Franz-JosefUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lindner, SimonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spitz, CharlotteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Franzmeier, NicolaiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baumann, KarlheinzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rominger, AxelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bartenstein, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ziegler, SibylleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Drzezga, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Respondek, GesineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buerger, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perneczky, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Levin, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoeglinger, Guenter U.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herms, JochenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haass, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brendel, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-602667
DOI: 10.1126/scitranslmed.abe5640
Journal or Publication Title: Sci. Transl. Med.
Volume: 13
Number: 615
Date: 2021
Publisher: AMER ASSOC ADVANCEMENT SCIENCE
Place of Publication: WASHINGTON
ISSN: 1946-6242
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ALZHEIMERS-DISEASE; AMYLOID DEPOSITION; TRANSGENIC MICE; MOUSE MODEL; BETA; METABOLISM; BRAIN; PROTEIN; AGEMultiple languages
Cell Biology; Medicine, Research & ExperimentalMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60266

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