Imperial College London
Alternate

DrRobinTyacke

Faculty of Medicine, Department of Brain Sciences

Research Manager
 
 
 
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Contact

 

+44 (0)20 7594 7096r.tyacke

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Mirzaei:2016,
author = {Mirzaei, N and Tang, S and Ashworth, S and Coello, C and Pilsson, C and Passchier, J and Selvaraj, V and Tyacke, R and Nutt, D and Sastre, M},
journal = {GLIA},
title = {In vivo Imaging of microglial activation by positron emission tomography with [11C]PBR28 in the 5XFAD model of Alzheimer’s disease},
url = {http://hdl.handle.net/10044/1/30664},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Microglial activation has been linked with deficits in neuronal function and synaptic plasticity inAlzheimer’s disease (AD). The mitochondrial translocator protein (TSPO) is known to be upregulatedin reactive microglia. Accurate visualization and quantification of microglial density by PET imagingusing the TSPO tracer [11C]-R-PK11195 has been challenging due to the limitations of the ligand. Inthis study, we aimed to evaluate the new TSPO tracer [11C]PBR28 as a marker for microglialactivation in the 5XFAD transgenic mouse model of AD. Dynamic PET scans were acquired followingintravenous administration of [11C]PBR28 in 6 month old 5XFAD mice and in wild-type controls.Autoradiography with [3H]PBR28 was carried out in the same brains to further confirm thedistribution of the radioligand. In addition, immunohistochemistry was performed on adjacent brainsections of the same mice to evaluate the co-localization of TSPO with microglia. PET imagingrevealed that brain uptake of [11C]PBR28 in 5XFAD mice was increased compared with control mice.Moreover, binding of [3H]PBR28, measured by autoradiography, was enriched in cortical andhippocampal brain regions, coinciding with the positive staining of the microglial marker Iba-1 andamyloid deposits in the same areas. Furthermore, double-staining using antibodies against TSPOdemonstrated co-localization of TSPO with microglia and not with astrocytes in 5XFAD mice andhuman post-mortem AD brains. Our data provide support of the suitability of [11C]PBR28 as a tool forin vivo monitoring of microglial activation and assessment of treatment response in future studiesusing animal models of AD.
AU  - Mirzaei,N
AU  - Tang,S
AU  - Ashworth,S
AU  - Coello,C
AU  - Pilsson,C
AU  - Passchier,J
AU  - Selvaraj,V
AU  - Tyacke,R
AU  - Nutt,D
AU  - Sastre,M
PY  - 2016///
SN  - 0894-1491
TI  - In vivo Imaging of microglial activation by positron emission tomography with [11C]PBR28 in the 5XFAD model of Alzheimer’s disease
T2  - GLIA
UR  - http://hdl.handle.net/10044/1/30664
ER  -
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