In vivo Imaging of microglial activation by positron emission tomography with [11C]PBR28 in the 5XFAD model of Alzheimer’s disease

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Title: In vivo Imaging of microglial activation by positron emission tomography with [11C]PBR28 in the 5XFAD model of Alzheimer’s disease
Author(s): Mirzaei, N
Tang, S
Ashworth, S
Coello, C
Pilsson, C
Passchier, J
Selvaraj, V
Tyacke, R
Nutt, D
Sastre, M
Item Type: Journal Article
Abstract: Microglial activation has been linked with deficits in neuronal function and synaptic plasticity in Alzheimer’s disease (AD). The mitochondrial translocator protein (TSPO) is known to be upregulated in reactive microglia. Accurate visualization and quantification of microglial density by PET imaging using the TSPO tracer [11C]-R-PK11195 has been challenging due to the limitations of the ligand. In this study, we aimed to evaluate the new TSPO tracer [11C]PBR28 as a marker for microglial activation in the 5XFAD transgenic mouse model of AD. Dynamic PET scans were acquired following intravenous 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 the distribution of the radioligand. In addition, immunohistochemistry was performed on adjacent brain sections of the same mice to evaluate the co-localization of TSPO with microglia. PET imaging revealed 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 and hippocampal brain regions, coinciding with the positive staining of the microglial marker Iba-1 and amyloid deposits in the same areas. Furthermore, double-staining using antibodies against TSPO demonstrated co-localization of TSPO with microglia and not with astrocytes in 5XFAD mice and human post-mortem AD brains. Our data provide support of the suitability of [11C]PBR28 as a tool for in vivo monitoring of microglial activation and assessment of treatment response in future studies using animal models of AD.
Date of Acceptance: 8-Feb-2016
URI: http://hdl.handle.net/10044/1/30664
ISSN: 0894-1491
Publisher: Wiley
Journal / Book Title: GLIA
Sponsor/Funder: Alzheimer's Research UK (ARUK)
Funder's Grant Number: ARUK-PPG2012B-21
Keywords: Neurology & Neurosurgery
1109 Neurosciences
Publication Status: Accepted
Appears in Collections:Department of Medicine
Faculty of Medicine



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