TY  - JOUR
AU  - Xiang, Xianyuan
AU  - Wind, Karin
AU  - Wiedemann, Thomas
AU  - Blume, Tanja
AU  - Shi, Yuan
AU  - Briel, Nils
AU  - Beyer, Leonie
AU  - Biechele, Gloria
AU  - Eckenweber, Florian
AU  - Zatcepin, Artem
AU  - Lammich, Sven
AU  - Ribicic, Sara
AU  - Tahirovic, Sabina
AU  - Willem, Michael
AU  - Deussing, Maximilian
AU  - Palleis, Carla
AU  - Rauchmann, Boris-Stephan
AU  - Gildehaus, Franz-Josef
AU  - Lindner, Simon
AU  - Spitz, Charlotte
AU  - Franzmeier, Nicolai
AU  - Baumann, Karlheinz
AU  - Rominger, Axel
AU  - Bartenstein, Peter
AU  - Ziegler, Sibylle
AU  - Drzezga, Alexander
AU  - Respondek, Gesine
AU  - Buerger, Katharina
AU  - Perneczky, Robert
AU  - Levin, Johannes
AU  - Höglinger, Günter U.
AU  - Herms, Jochen
AU  - Haass, Christian
AU  - Brendel, Matthias
TI  - Microglial activation states drive glucose uptake and FDG-PET alterations in neurodegenerative diseases
JO  - Science translational medicine
VL  - 13
IS  - 615
SN  - 1946-6234
CY  - Washington, DC
PB  - AAAS
M1  - FZJ-2021-05946
SP  - eabe5640
PY  - 2021
AB  - 2-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.
LB  - PUB:(DE-HGF)16
C6  - 34644146
UR  - <Go to ISI:>//WOS:000707525800003
DO  - DOI:10.1126/scitranslmed.abe5640
UR  - https://juser.fz-juelich.de/record/904376
ER  -