Astrocytic TSPO upregulation appears before microglial TSPO in Alzheimer’s disease
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Date
2020-06-30
Journal Title
Journal ISSN
Volume Title
Publisher
IOS Press
Abstract
Background:
In vivo PET/SPECT imaging of neuroinflammation is primarily based on the estimation of the 18 kDa-rranslocator-protein (TSPO). However, TSPO is expressed by different cell types which complicates the interpretation.
Objective:
The present study evaluates the cellular origin of TSPO alterations in Alzheimer’s disease (AD).
Methods:
The TSPO cell origin was evaluated by combining radioactive imaging approaches using the TSPO radiotracer [125I]CLINDE and fluorescence-activated cell sorting, in a rat model of AD (TgF344-AD) and in AD subjects.
Results:
In the hippocampus of TgF344-AD rats, TSPO overexpression not only concerns glial cells but the increase is visible at 12 and 24 months in astrocytes and only at 24 months in microglia. In the temporal cortex of AD subjects, TSPO upregulation involved only glial cells. However, the mechanism of this upregulation appears different with an increase in the number of TSPO binding sites per cell without cell proliferation in the rat, and a microglial cell population expansion with a constant number of binding sites per cell in human AD.
Conclusion:
These data indicate an earlier astrocyte intervention than microglia and that TSPO in AD probably is an exclusive marker of glial activity without interference from other TSPO-expressing cells. This observation indicates that the interpretation of TSPO imaging depends on the stage of the pathology, and highlights the particular role of astrocytes. © 2020 IOS Press and the authors. Open Access CC BY-NC 4.0
Description
This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution Non-Commercial License (CC BY-NC 4.0).
Keywords
Nervous system diseases, Inflammation, Tracer techniques, Fluorescence, Cerebral cortex, Rats
Citation
Tournier, B. B., Tsartsalis, S., Ceyzériat, K., Fraser, B. H., Grégoire, M.-C., Kövari, E. & Millet, P. (2020). Astrocytic TSPO upregulation appears before microglial TSPO in Alzheimer’s disease. Journal of Alzheimer's Disease, 77, 3, 1043-1056 1-14. doi:10.3233/JAD-200136