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Cited by 126Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

Characterization of the 18 kDa translocator protein (TSPO) expression in post‐mortem normal and Alzheimer's disease brains

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Gui, Yaxing, Marks, Jordan D., Das, Sudeshna, Hyman, Bradley T., Serrano‐Pozo, Alberto·2020·Brain Pathology
DOI 10.1111/bpa.12763PMC PMC6904423
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Abstract

The 18 kDa translocator protein (TSPO) is a widely used target for microglial PET imaging radioligands, but its expression in post‐mortem normal and diseased human brain is not well described. We aimed at characterizing the TSPO expression in human control (CTRL) and Alzheimer's disease (AD) brains. Specifically, we sought to: (1) define the cell type(s) expressing TSPO; (2) compare tspo mRNA and TSPO levels between AD and CTRL brains; (3) correlate TSPO levels with quantitative neuropathological measures of reactive glia and AD neuropathological changes; and (4) investigate the effects of the TSPO rs6971 SNP on tspo mRNA and TSPO levels, glial responses and AD neuropathological changes. We performed quantitative immunohistochemistry and Western blot in post‐mortem brain samples from CTRL and AD subjects, as well as analysis of publicly available mouse and human brain RNA‐Seq datasets. We found that: (1) TSPO is expressed not just in microglia, but also in astrocytes, endothelial cells and vascular smooth muscle cells; (2) there is substantial overlap of tspo mRNA and TSPO levels between AD and CTRL subjects and in TSPO levels between temporal neocortex and white matter in both groups; (3) TSPO cortical burden does not correlate with the burden of activated microglia or reactive astrocytes, Aβ plaques or neurofibrillary tangles, or the cortical thickness; (4) the TSPO rs6971 SNP does not significantly impact tspo mRNA or TSPO levels, the magnitude of glial responses, the cortical thickness, or the burden of AD neuropathological changes. These results could inform ongoing efforts toward the development of reactive glia‐specific PET radioligands.

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  • TSPO is expressed in almost all CNS cells, including astrocytes, neurons and endothelial cells.

    “Although increased TSPO expression has historically been mostly associated with microglial activation, TSPO is now known to be expressed in almost all CNS cells including astrocytes, neurons and endothelial cells [21–27], all of which may also be involved in, or be affected by neuroinflammation [28].”

    From Pharmacological modulation of TSPO in microglia/macrophages and neurons in a chronic neurodegenerative model of prion disease (2023) · cites this paper as [27]

    The Results section confirms TSPO expression in astrocytes and endothelial cells, but reports that neuronal-marker staining showed no TSPO expression in neurons. That directly contradicts the claim’s inclusion of neurons among TSPO-expressing CNS cells. (LLM, conf=0.90)

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  • In postmortem human Alzheimer's disease brains, 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 [27]

    The Results section identifies TSPO-positive microglia, astrocytes, and endothelial cells in human brain tissue. It reports a modest increase in overall TSPO immunoreactivity in AD white matter, but does not show that TSPO-positive cells of each of the three types increased; the Conclusions instead emphasize substantial overlap in TSPO levels between AD and controls. Page numbers were not available in our copy. (LLM, conf=0.88)

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Cited by

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Authors
Gui, Y., Marks, J. D., Das, S., Hyman, B. T., & Serrano‐Pozo, A.
Affiliations
  • Sir Run Run Shaw Hospital (CN)
  • Massachusetts General Hospital (US)
  • Harvard University (US)
Corresponding author
Serrano‐Pozo, Alberto
ORCID
Venue
Brain Pathology
Publisher
Wiley
Published
2019-07-25
Volume
30
Issue
1
Pages
151-164
ISSN
  • 1015-6305 (ISSN-L)
  • 1750-3639
DOI
10.1111/bpa.12763
PMC
PMC6904423
OpenAlex
W2956009998
Cited by
126
References
11
Citations by year
2026: 11 · 2025: 16 · 2024: 23 · 2023: 19 · 2022: 17 · 2021: 24 · 2020: 14 · 2019: 2
FWCI
6.27
Type
journal article
Language
en
Open access
Licence
Locations
  • Brain Pathology (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • National Institute of Neurological Disorders and Stroke (R25NS065743)
  • Alzheimer's Association (AACF-17-524184)
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, microglia, reactive astrocytes, glial activation, cortical thickness, amyloid plaques, neurofibrillary tangles, PET radiotracer, postmortem brain, astrocytes, vascular smooth muscle cells, endothelial cells
MeSH terms
Alzheimer Disease, Astrocytes, Autopsy, Brain, Humans, Longitudinal Studies, Neuroglia, Gene Expression, Neurofibrillary Tangles, Microglia, Receptors, GABA, Endothelial Cells, Positron-Emission Tomography, Plaque, Amyloid, Transcriptome

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