TSPO and amyloid deposits in sub-regions of the hippocampus in the 3xTgAD mouse model of Alzheimer’s disease
Open accessAbstract
The involvement of the 18kDa translocator protein (TSPO), a marker of neuroinflammation, in Alzheimer's disease (AD) remains controversial. In the present report, we used [125 I]-CLINDE, a SPECT TSPO radiotracer never before used in AD, and we investigated the relationship between TSPO and amyloid plaque density (using [125 I]-DRM106) in a triple transgenic mouse model of AD (3xTgAD, APP SWE, PS1 M146V and Tau P301L). Our results show that TSPO increases appear before those of amyloid deposits. Moreover, the different parts of the hippocampus are differentially affected. Indeed, for both TSPO and amyloid, the subiculum is affected earlier and the ventral hippocampus later than the dorsal hippocampus. In the subiculum and the dorsal hippocampus of 3xTgAD mice, a positive correlation between TSPO and of amyloid deposit levels is observed. This data supports the hypothesis that TSPO could be used as a predictive marker of amyloid pathology. In addition, our immunohistochemical data shows a segregation of TSPO in the hippocampus and immunofluorescence imaging revealed a mainly microglial origin of the TSPO expression. Thus, imaging TSPO with CLINDE may be a good alternative to PET radiotracers.
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In models of Alzheimer's-like neurodegeneration, TSPO positive microglia, astrocytes and endothelium are all increased.
“Similarly, others have found that TSPO positive microglia, astrocytes and endothelium are all increased in models of Alzheimer’s-like neurodegeneration [48–51] and in postmortem human Alzheimer’s disease brains [27].”
From Pharmacological modulation of TSPO in microglia/macrophages and neurons in a chronic neurodegenerative model of prion disease (2023) · cites this paper as [50]
The Discussion (p. 20) reports elevated TSPO colocalization with microglia in 3xTgAD mice, with some TSPO expression in astrocytes. It does not establish that TSPO-positive astrocytes increased. The endothelial finding (pp. 17, 21) concerns TSPO-positive cells in human choroid plexus, not an increase in an Alzheimer’s-like mouse model. (LLM, conf=0.88)
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In Vivo TSPO Signal and Neuroinflammation in Alzheimer’s Disease
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- Authors
- Tournier, B. B., Tsartsalis, S., Rigaud, D., Fossey, C., Cailly, T., Fabis, F., Pham, T., Grégoire, M.-C., Kövari, E., Moulin-Sallanon, M., Savioz, A., & Millet, P.
- Affiliations
- University Hospital of Geneva (CH)
- Normandie Université (FR)
- Australian Nuclear Science and Technology Organisation (AU)
- University of Geneva (CH)
- Corresponding author
- Millet, Philippe
- ORCID
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2019-01
- Volume
- 121
- Pages
- 95-105
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2893467874
- Cited by
- 62
- References
- 13
- Citations by year
- 2025: 9 · 2024: 6 · 2023: 9 · 2022: 10 · 2021: 15 · 2020: 8 · 2019: 4 · 2018: 1
- FWCI
- 4.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (acceptedVersion, other-oa)
- HAL (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by-nc-nd)
- Funders
- University of California
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- translocator protein (TSPO), amyloid plaques, Alzheimer's disease, hippocampus, subiculum, dorsal hippocampus, ventral hippocampus, neuroinflammation, microglia, SPECT imaging
- MeSH terms
- Alzheimer Disease, Animals, Choroid Plexus, Disease Models, Animal, Encephalitis, Female, Hippocampus, Humans, Mice, Inbred C57BL, Mice, Transgenic, Tomography, Emission-Computed, Single-Photon, Receptors, GABA, Plaque, Amyloid
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