Astrocytic TSPO upregulation appears before microglial TSPO in Alzheimer’s disease

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dc.contributor.authorTournier, BBen_AU
dc.contributor.authorTsartsalis, Sen_AU
dc.contributor.authorCeyzériat, Ken_AU
dc.contributor.authorFraser, BHen_AU
dc.contributor.authorGrégoire, MCen_AU
dc.contributor.authorKövari, Een_AU
dc.contributor.authorMillet, Pen_AU
dc.date.accessioned2021-09-08T06:01:15Zen_AU
dc.date.available2021-09-08T06:01:15Zen_AU
dc.date.issued2020-06-30en_AU
dc.date.statistics2021-09-07en_AU
dc.descriptionThis 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).en_AU
dc.description.abstractBackground: 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 4.0en_AU
dc.identifier.citationTournier, 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-200136en_AU
dc.identifier.issn1875-8908en_AU
dc.identifier.issue3en_AU
dc.identifier.journaltitleJournal of Alzheimer's Diseaseen_AU
dc.identifier.pagination1043-1056en_AU
dc.identifier.urihttps://doi.org/10.3233/JAD-200136en_AU
dc.identifier.urihttps://apo.ansto.gov.au/dspace/handle/10238/11639en_AU
dc.identifier.volume77en_AU
dc.language.isoenen_AU
dc.publisherIOS Pressen_AU
dc.subjectNervous system diseasesen_AU
dc.subjectInflammationen_AU
dc.subjectTracer techniquesen_AU
dc.subjectFluorescenceen_AU
dc.subjectCerebral cortexen_AU
dc.subjectRatsen_AU
dc.titleAstrocytic TSPO upregulation appears before microglial TSPO in Alzheimer’s diseaseen_AU
dc.typeJournal Articleen_AU
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