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Imaging of Microglial Activation in Alzheimer’s Disease by [11C]PBR28 PET

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Biomarkers for Alzheimer’s Disease Drug Development

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1750))

Abstract

Deficits in neuronal function and synaptic plasticity in Alzheimer’s disease (AD) are believed to be linked to microglial activation. A hallmark of reactive microglia is the upregulation of mitochondrial translocator protein (TSPO) expression. Positron emission tomography (PET) is a nuclear imaging technique that measures the distribution of trace doses of radiolabeled compounds in the body over time. PET imaging using the 2nd generation TSPO tracer [11C]PBR28 provides an opportunity for accurate visualization and quantification of changes in microglial density in transgenic mouse models of Alzheimer’s disease (AD). Here, we describe the methodology for the in vivo use of [11C]PBR28 in AD patients and the 5XFAD transgenic mouse model of AD and compare the results against healthy individuals and wild-type controls. To confirm the results, autoradiography with [3H]PBR28 and immunochemistry was carried out in the same mouse brains. Our data shows that [11C]PBR28 is suitable as a tool for in vivo monitoring of microglial activation and may be useful to assess treatment response in future studies.

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Authors and Affiliations

  1. Division of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK

    Cornelius K. Donat, Nazanin Mirzaei, Paul Edison & Magdalena Sastre

  2. Imanova Limited, London, UK

    Sac-Pham Tang

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  1. Cornelius K. Donat
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  2. Nazanin Mirzaei
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  3. Sac-Pham Tang
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  4. Paul Edison
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  5. Magdalena Sastre
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Correspondence to Magdalena Sastre .

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  1. Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität München, Munich, Germany

    Robert Perneczky

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Donat, C.K., Mirzaei, N., Tang, SP., Edison, P., Sastre, M. (2018). Imaging of Microglial Activation in Alzheimer’s Disease by [11C]PBR28 PET. In: Perneczky, R. (eds) Biomarkers for Alzheimer’s Disease Drug Development. Methods in Molecular Biology, vol 1750. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7704-8_22

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  • DOI: https://doi.org/10.1007/978-1-4939-7704-8_22

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