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Cited by 65Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

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

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Tournier, Benjamin B., Tsartsalis, Stergios, Ceyzériat, Kelly, Fraser, Ben H., Grégoire, Marie-Claude, Kövari, Enikö, Millet, Philippe·2020·Journal of Alzheimer’s Disease
DOI 10.3233/jad-200136PMC PMC7683091
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Abstract

Background: In vivo PET/SPECT imaging of neuroinflammation is primarily based on the estimation of the 18 kDa-translocator-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 [ 125 I]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.

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Authors
Tournier, B. B., Tsartsalis, S., Ceyzériat, K., Fraser, B. H., Grégoire, M.-C., Kövari, E., & Millet, P.
Affiliations
  • University Hospital of Geneva (CH)
  • Australian Nuclear Science and Technology Organisation (AU)
  • Division of Geriatric Psychiatry, Department of Mental Health and Psychiatry, University Hospitals of Geneva, Switzerland
  • University of Geneva (CH)
Corresponding author
Millet, Philippe
ORCID
Venue
Journal of Alzheimer’s Disease
Publisher
SAGE Publications
Published
2020-08-14
Volume
77
Issue
3
Pages
1043-1056
ISSN
  • 1387-2877 (ISSN-L)
  • 1875-8908
DOI
10.3233/jad-200136
PMC
PMC7683091
OpenAlex
W3049257001
Cited by
65
References
22
Citations by year
2026: 3 · 2025: 14 · 2024: 11 · 2023: 13 · 2022: 12 · 2021: 10 · 2020: 2
FWCI
3.58
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Alzheimer s Disease (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
  • The Australian Nuclear Science and Technology Organisation Institutional Repository (The Australian Nuclear Science and Technology Organisation) (submittedVersion, cc-by-nc)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by-nc)
Funders
  • National Science Foundation
  • Velux Stiftung (project n. 1123)
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (184713, 320030)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
translocator protein (TSPO), Alzheimer's disease
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Animals, Astrocytes, Female, Hippocampus, Humans, Male, Rats, Inbred F344, Up-Regulation, Microglia, Receptors, GABA, Rats, Rats, Transgenic

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Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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