The microglial translocator protein (TSPO) in Alzheimer's disease reflects a phagocytic phenotype
The microglial translocator protein (TSPO) in Alzheimer's disease reflects a phagocytic phenotype
Translocator protein (TSPO) is a mitochondrial protein expressed by microglia, ligands for which are used as a marker of neuroinflammation in PET studies of Alzheimer's disease (AD). We previously showed increasing TSPO load in the cerebral cortex with AD progression, consistent with TSPO PET scan findings. Here, we aim to characterise the microglial phenotype associated with TSPO expression to aid interpretation of the signal generated by TSPO ligands in patients. Human post-mortem sections of temporal lobe (TL) and cerebellum (Cb) from cases classified by Braak group (0-II, III-IV, V-VI; each n = 10) were fluorescently double labelled for TSPO and microglial markers: Iba1, HLA-DR, CD68, MSR-A and CD64. Quantification was performed on scanned images using QuPath software to assess the microglial phenotype of TSPO. Qualitative analysis was also performed for TSPO with GFAP (astrocytes), CD31 (endothelial cells) and CD163 (perivascular macrophages) to characterise the cellular profile of TSPO. The percentage of CD68
+TSPO
+ double-labelled cells was significantly higher than for other microglial markers in both brain regions and in all Braak stages, followed by MSR-A
+TSPO
+ microglia. Iba1
+TSPO
+ cells were more numerous in the cerebellum than the temporal lobe, while CD64
+TSPO
+ cells were more numerous in the temporal lobe. No differences were observed for the other microglial markers. TSPO expression was also detected in endothelial cells, but not detected in astrocytes nor in perivascular macrophages. Our data suggest that TSPO is mainly related to a phagocytic profile of microglia (CD68
+) in human AD, potentially highlighting the ongoing neurodegeneration.
Humans, Alzheimer Disease/pathology, Receptors, GABA/metabolism, Microglia/metabolism, Male, Female, Aged, Aged, 80 and over, Phagocytosis, Phenotype, Antigens, CD/metabolism, Cerebellum/pathology, Temporal Lobe/metabolism, Microfilament Proteins/metabolism, Antigens, Differentiation, Myelomonocytic/metabolism, Calcium-Binding Proteins
Garland, Emma F.
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Antony, Henrike
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Kulagowska, Laura
97aa0e3a-d4e5-4137-a845-850b2d2f5933
Scott, Thomas
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Rogien, Charlotte
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Bottlaender, Michel
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Nicoll, James A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
14 November 2024
Garland, Emma F.
b59c66f2-ac4c-4d8d-823d-687769deccce
Antony, Henrike
12e09f7c-a09a-40d2-b9d6-5d5d23be4763
Kulagowska, Laura
97aa0e3a-d4e5-4137-a845-850b2d2f5933
Scott, Thomas
651073ff-87d8-42a9-a25d-c2a663fcb449
Rogien, Charlotte
d4730050-edf1-4f6a-acb5-c827acfcdf19
Bottlaender, Michel
7ec76930-cf42-4f7b-8801-fbb3789eabed
Nicoll, James A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
Garland, Emma F., Antony, Henrike, Kulagowska, Laura, Scott, Thomas, Rogien, Charlotte, Bottlaender, Michel, Nicoll, James A.R. and Boche, Delphine
(2024)
The microglial translocator protein (TSPO) in Alzheimer's disease reflects a phagocytic phenotype.
Acta Neuropathologica, 148 (1), [62].
(doi:10.1007/s00401-024-02822-x).
Abstract
Translocator protein (TSPO) is a mitochondrial protein expressed by microglia, ligands for which are used as a marker of neuroinflammation in PET studies of Alzheimer's disease (AD). We previously showed increasing TSPO load in the cerebral cortex with AD progression, consistent with TSPO PET scan findings. Here, we aim to characterise the microglial phenotype associated with TSPO expression to aid interpretation of the signal generated by TSPO ligands in patients. Human post-mortem sections of temporal lobe (TL) and cerebellum (Cb) from cases classified by Braak group (0-II, III-IV, V-VI; each n = 10) were fluorescently double labelled for TSPO and microglial markers: Iba1, HLA-DR, CD68, MSR-A and CD64. Quantification was performed on scanned images using QuPath software to assess the microglial phenotype of TSPO. Qualitative analysis was also performed for TSPO with GFAP (astrocytes), CD31 (endothelial cells) and CD163 (perivascular macrophages) to characterise the cellular profile of TSPO. The percentage of CD68
+TSPO
+ double-labelled cells was significantly higher than for other microglial markers in both brain regions and in all Braak stages, followed by MSR-A
+TSPO
+ microglia. Iba1
+TSPO
+ cells were more numerous in the cerebellum than the temporal lobe, while CD64
+TSPO
+ cells were more numerous in the temporal lobe. No differences were observed for the other microglial markers. TSPO expression was also detected in endothelial cells, but not detected in astrocytes nor in perivascular macrophages. Our data suggest that TSPO is mainly related to a phagocytic profile of microglia (CD68
+) in human AD, potentially highlighting the ongoing neurodegeneration.
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s00401-024-02822-x
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Accepted/In Press date: 1 November 2024
Published date: 14 November 2024
Keywords:
Humans, Alzheimer Disease/pathology, Receptors, GABA/metabolism, Microglia/metabolism, Male, Female, Aged, Aged, 80 and over, Phagocytosis, Phenotype, Antigens, CD/metabolism, Cerebellum/pathology, Temporal Lobe/metabolism, Microfilament Proteins/metabolism, Antigens, Differentiation, Myelomonocytic/metabolism, Calcium-Binding Proteins
Identifiers
Local EPrints ID: 502158
URI: http://eprints.soton.ac.uk/id/eprint/502158
ISSN: 0001-6322
PURE UUID: 9f51a3d2-5862-464e-b40b-b0c11767a0ac
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Date deposited: 17 Jun 2025 16:53
Last modified: 22 Aug 2025 01:49
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Contributors
Author:
Emma F. Garland
Author:
Henrike Antony
Author:
Laura Kulagowska
Author:
Thomas Scott
Author:
Charlotte Rogien
Author:
Michel Bottlaender
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