Cited by 82Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsMedical Imaging Techniques and Applications

In vivo imaging of microglial activation by positron emission tomography with [11C]PBR28 in the 5XFAD model of A lzheimer's disease

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Mirzaei, Nazanin, Tang, Sac Pham, Ashworth, Sharon, Coello, Christopher, Plisson, Christophe, Passchier, Jan, Selvaraj, Vimal, Tyacke, Robin J. +2 more·2016·Glia

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 [11 C]‐R‐PK11195 has been challenging due to the limitations of the ligand. In this study, it was aimed to evaluate the new TSPO tracer [11 C]PBR28 as a marker for microglial activation in the 5XFAD transgenic mouse model of AD. Dynamic PET scans were acquired following intravenous administration of [11 C]PBR28 in 6‐month‐old 5XFAD mice and in wild‐type controls. Autoradiography with [3 H]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 [11 C]PBR28 in 5XFAD mice was increased compared with control mice. Moreover, binding of [3 H]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. The data provided support of the suitability of [11 C]PBR28 as a tool for in vivo monitoring of microglial activation and assessment of treatment response in future studies using animal models of AD. GLIA 2016;64:993–1006

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Crossref · 10.1002/glia.22978

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Authors
Mirzaei, N., Tang, S. P., Ashworth, S., Coello, C., Plisson, C., Passchier, J., Selvaraj, V., Tyacke, R. J., Nutt, D. J., & Sastre, M.
Affiliations
  • Imperial College London (GB)
  • Imanova Limited Du Cane Road London W12 0NN United Kingdom
  • Cornell University (US)
Corresponding author
  • Tyacke, Robin J.
  • Sastre, Magdalena
Venue
Glia
Publisher
Wiley
Published
2016-03-09
Volume
64
Issue
6
Pages
993-1006
ISSN
  • 0894-1491 (ISSN-L)
  • 1098-1136
OpenAlex
W2294606443
Cited by
82
References
83
Citations by year
2026: 2 · 2025: 5 · 2024: 3 · 2023: 2 · 2022: 12 · 2021: 10 · 2020: 9 · 2019: 12 · 2018: 11 · 2017: 13 · 2016: 3
FWCI
7.12
Type
journal article
Language
en
Open access
Locations
  • Glia (publishedVersion)
  • PubMed (publishedVersion)
  • Spiral (Imperial College London) (submittedVersion, cc-by-nc-nd)
Funders
Alzheimer’s Research UK (ARUK‐PPG2012B‐21)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
Keywords
microglial activation, Alzheimer's disease, [11C]PBR28, translocator protein (TSPO), 5xFAD mice, positron emission tomography, amyloid deposits, Iba1, radioligand binding, hippocampus
MeSH terms
Alzheimer Disease, Animals, Astrocytes, Brain, Disease Models, Animal, Mice, Transgenic, Microglia, Receptors, GABA, Positron-Emission Tomography, Mice

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