Journal Article

FZJ-2021-05946

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Microglial activation states drive glucose uptake and FDG-PET alterations in neurodegenerative diseases

Xiang, X. (Corresponding author) ; Wind, K. ; Wiedemann, T. ; Blume, T. ; Shi, Y. ; Briel, N. ; Beyer, L. ; Biechele, G. ; Eckenweber, F. ; Zatcepin, A. ; Lammich, S. ; Ribicic, S. ; Tahirovic, S. ; Willem, M. ; Deussing, M. ; Palleis, C. ; Rauchmann, B.-S. ; Gildehaus, F.-J. ; Lindner, S. ; Spitz, C. ; Franzmeier, N. ; Baumann, K. ; Rominger, A. ; Bartenstein, P. ; Ziegler, S. ; Drzezga, A.FZJ* ; Respondek, G. ; Buerger, K. ; Perneczky, R. ; Levin, J. ; Höglinger, G. U. ; Herms, J. ; Haass, C. ; Brendel, M.

2021
AAAS Washington, DC

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Please use a persistent id in citations: http://hdl.handle.net/2128/32257  doi:10.1126/scitranslmed.abe5640

Abstract: 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.

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Contributing Institute(s):

1. Molekulare Organisation des Gehirns (INM-2)

Research Program(s):

1. 5253 - Neuroimaging (POF4-525) (POF4-525)

Appears in the scientific report 2022

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Database coverage:
; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Essential Science Indicators ; IF >= 15 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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